what are two of the major classes of antidepressant drugs

The most important classes of antidepressants are the selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), tetracyclic antidepressants (TeCAs), and noradrenergic and specific serotonergic antidepressant (NaSSAs).[3] St John's wort is also used in the treatment of depression.[3][4]

Antidepressant

Antidepressants are drugs used for the treatment of major depressive disorder and other conditions, including dysthymia, anxiety disorders, obsessive–compulsive disorder, eating disorders, chronic pain, neuropathic pain and, in some cases, dysmenorrhoea, snoring, migraine, attention-deficit hyperactivity disorder (ADHD), addiction, dependence, and sleep disorders. They may be prescribed alone or in combination with other medications.

Some typical side effects of antidepressants are dry mouth, weight gain, and lack of sex drive. Some antidepressants may even cause infertility within both males and females depending on the extent of how long the medication was taken or how the body reacted to the medicine.[1] Most types of antidepressants are typically safe to take, but may cause increased thoughts of suicide when taken by children, adolescents, and young adults.[2] When prescribing antidepressants, doctors will warn individuals not to abruptly stop taking the medication or miss several doses at one time; this could cause major withdrawal-like symptoms, and quitting the medication suddenly can worsen the depression. Patients are instead encouraged to communicate and work with their doctors to wean themselves off the medication by gradually and safely decreasing the dosage when needed.[1]

One theory regarding the cause of depression is that it is characterized by an overactive hypothalamic–pituitary–adrenal axis (HPA axis) that resembles the neuro-endocrine response to stress. These HPA axis abnormalities participate in the development of depressive symptoms, and antidepressants may serve to regulate HPA axis function.[5]

There has been a long debate in the medical community about the effectiveness of antidepressants, centering around whether the observed results in patients can be attributed to the placebo effect.[6]

For depression, the Hamilton Depression Rating Scale (HAM-D) is often used to measure the severity of depression.[7] The maximum score for the 17-item HAM-D questionnaire is 52; the higher the score, the more severe the depression.

The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. The guidelines recommended that antidepressant treatment be considered for:

The guidelines further note that antidepressant treatment should be used in combination with psychosocial interventions in most cases, should be continued for at least six months to reduce the risk of relapse, and that SSRIs are typically better tolerated than other antidepressants.[8]

American Psychiatric Association treatment guidelines recommend that initial treatment should be individually tailored based on factors that include severity of symptoms, co-existing disorders, prior treatment experience, and patient preference. Options may include pharmacotherapy, psychotherapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or light therapy. They recommended antidepressant medication as an initial treatment choice in people with mild, moderate, or severe major depression, that should be given to all patients with severe depression unless ECT is planned.[9]

Conflicting results have arisen from studies analyzing the efficacy of antidepressants by comparisons to placebo in people with acute mild to moderate depression. Stronger evidence supports the usefulness of antidepressants in the treatment of depression that is chronic (dysthymia) or severe.

A 2018 meta-analysis of trials found that in adults with major depressive disorder antidepressants were more efficacious than placebo [10] Effect sizes measured at 8-weeks after treatment onset were modest with a summary standard mean difference[11] of 0.3.

A 2017 meta analysis comparing the efficacy of SSRIs against placebo found the mean reduction in Hamilton Depression Rating Scale (HDRS) to be -1.94 points over 49 studies. This was statistically significant, but failed to meet the clinical significance threshold, predefined according to the National Institute for Health and Care Excellence recommended standard mean difference of 0.5, equivalent to a 3-point reduction in HDRS. A high risk of bias was found, which could possibly explain the statistically significant effect of SSRI, and the authors concluded that the frequency of adverse events outweighed the small clinical improvements.[12]

A 2015 systematic review of add-on therapies for treatment-resistant depression concluded that quetiapine and aripiprazole have the strongest evidence-base supporting their efficacy, but they are associated with additional treatment-related side effects when used as an add-on therapy.[13]

In 2014 the U.S. FDA published a systematic review of all antidepressant maintenance trials submitted to the agency between 1985 and 2012. The authors concluded that maintenance treatment reduced the risk of relapse by 52% compared to placebo, and that this effect was primarily due to recurrent depression in the placebo group rather than a drug withdrawal effect.[14]

A 2012 meta-analysis found that fluoxetine and venlafaxine were effective for major depression in all age groups. The authors also found no evidence of a relationship between baseline severity of depression and degree of benefit of antidepressants over placebo.[15]

A review published in 2012 found a negative correlation between study year and efficacy of antidepressants as measured by response rate. The change in response rate was largely driven by increase in placebo response. However the authors still concluded that antidepressants were effective in treating depression.[16] The authors found that TCAs were the most effective drug, followed by SNRIs, MAOIs, SSRIs and atypical antidepressants.

The Cochrane Collaboration published a systematic review of clinical trials of the tricyclic antidepressant amitriptyline in 2012. The study concluded that in spite of moderate evidence for publication bias, there is strong evidence that the efficacy of amitriptyline is superior to placebo.[17]

The efficacy of paroxetine (Paxil) and imipramine was observed in a 2010 meta analysis to be dependent upon the baseline severity, as measured by the HDRS. Antidepressants in patients with a score less than 23(indicating mild to moderate depression) demonstrated a small benefit over placebo. However, antidepressants in those with a score >25 exhibited an advantage over placebo that cross the NICE threshold for clinical significance.[18]

A review commissioned by the National Institute for Health and Care Excellence that published in 2009 concluded that there is strong evidence that SSRIs have greater efficacy than placebo on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression. The treatment guidelines developed in conjunction with this review suggest that antidepressants should be considered in patients with moderate to severe depression and those with mild depression that is persistent or resistant to other treatment modalities.[19]

A 2008 Cochrane Collaboration review on St John's wort (specifically, any extracts which contain Hypericum perforatum), and a 2015 meta-analytic systematic review by some of the same authors, both concluded that it: has superior efficacy to placebo in treating depression; is as effective as standard antidepressant pharmaceuticals for treating depression; and has fewer adverse effects than other antidepressants. The 2015 meta analysis concluded that it is difficult to assign a place for St. John's wort in the treatment of depression owing to limitations in the available evidence base, including large variations in efficacy seen in trials performed in German-speaking relative to other countries.[3][4] Reversible inhibitors of monoamine oxidase A (RIMAs) have also been shown to be an effective drug therapy with greater tolerability than other antidepressants;[3] however, the efficacy of SSRIs, tricyclic, and tetracyclic antidepressants in treating depression is supported by a much larger evidence base compared to other antidepressant drug therapies (i.e., St John's wort, rMAO-A inhibitors, serotonin–norepinephrine reuptake inhibitor, serotonin antagonist and reuptake inhibitors, noradrenaline reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants).[3]

In a 2008 publication, Irving Kirsch and Thomas Moore concluded that the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance.[20] This updated work they had first published in 2002 in which they stated that the evidence is most consistent a role as active placebos.[21]

A 2004 review concluded that antidepressant studies that failed to support efficacy claims were dramatically less likely to be published than those that did support favorable efficacy claims.[22] Similar results were obtained for a study of publication of clinical trials of antidepressants in children.[23] A 2015 investigation of meta-analyses of antidepressant studies found that 79% of them had "sponsorship or authors who were (pharmaceutical) industry employees and/or had conflicts of interest".[24]

A study published in the Journal of the American Medical Association (JAMA) in 2002 demonstrated that the magnitude of the placebo effect in clinical trials of depression have been growing over time, while the effect size of tested drugs has remained relatively constant. The authors suggest that one possible explanation for the growing placebo effect in clinical trials is the inclusion of larger number of participants with shorter term, mild, or spontaneously remitting depression as a result of decreasing stigma associated with antidepressant use.[25] Placebo response rates in clinical trials of complementary and alternative (CAM) therapies are significantly lower than those in clinical trials of traditional antidepressants.[26]

The largest and most expensive study conducted to date, on the effectiveness of pharmacological treatment for depression, was commissioned by the National Institute of Mental Health.[27] The study was dubbed "The Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) Study. The results[28][29] are summarized here. Participants in the trial were recruited when they sought medical care at general medical or psychiatric clinics. No advertising was used to recruit subjects in order to maximize the generalizability of the study results. Participants were required to have a minimum score of 14 point on the Hamilton Depression Scale (HAM-D17) in order to be enrolled in the trial. Generally accepted cutoffs are 7–17 points for mild depression, 18–24 points for moderate depression, and ≥ 24 for severe depression.[30] The average participant baseline HAM-D17 score was 22.[31] The pre-specified primary endpoint of this trial was remission as determined by the HAM-D score, with all patients with missing scores rated as non-responders. In the aftermath of the trial, the investigators have presented the results mainly using the secondary endpoint of remission according to the QIDS-SR16 Score, which tend to be somewhat higher.

There were no statistical or meaningful clinical differences in remission rates, response rates, or times to remission or response among any of the medications compared in this study.[36] These included bupropion sustained release, bupropion, citalopram, lithium, mirtazapine, nortriptyline, sertraline, triiodothyronine, tranylcypromine, and venlafaxine extended release.[medical citation needed]

A 2008 review of randomized controlled trials concluded that symptomatic improvement with SSRIs was greatest by the end of the first week of use, but that some improvement continued for at least 6 weeks.[37]

Between 30% and 50% of individuals treated with a given antidepressant do not show a response.[38][39] In clinical studies, approximately one-third of patients achieve a full remission, one-third experience a response and one-third are nonresponders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, psychic anxiety, sleep disturbance, fatigue and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates 3–6 times higher in patients with residual symptoms than in those who experience full remission.[40] In addition, antidepressant drugs tend to lose efficacy over the course of treatment.[41] According to data from the Centers for Disease Control and Prevention, less than one-third of Americans taking one antidepressant medication have seen a mental health professional in the previous year.[42] A number of strategies are used in clinical practice to try to overcome these limits and variations.[43] They include switching medication, augmentation, and combination.

The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved following six to eight weeks of treatment with an antidepressant, to switch to an antidepressant in the same class, then to a different class of antidepressant. A 2006 meta-analysis review found wide variation in the findings of prior studies; for patients who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug. However, the more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial.[39] However, a later meta-analysis found no difference between switching to a new drug and staying on the old medication; although 34% of treatment resistant patients responded when switched to the new drug, 40% responded without being switched.[44]

For a partial response, the American Psychiatric Association guidelines suggest augmentation, or adding a drug from a different class. These include lithium and thyroid augmentation, dopamine agonists, sex steroids, NRIs, glucocorticoid-specific agents, or the newer anticonvulsants.[45]

A combination strategy involves adding another antidepressant, usually from a different class so as to have effect on other mechanisms. Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy.[46] Other tests recently conducted include the use of psychostimulants as an augmentation therapy. Several studies have shown the efficacy of combining modafinil to treatment-resistant patients. It has been used to help combat SSRI-associated fatigue.[47]

The therapeutic effects of antidepressants typically do not continue once the course of medication ends. This results in a high rate of relapse. A 2003 meta-analysis of 31 placebo-controlled antidepressant trials, mostly limited to studies covering a period of one year, found that 18% of patients who had responded to an antidepressant relapsed while still taking it, compared to 41% whose antidepressant was switched for a placebo.[48]

A gradual loss of therapeutic benefit occurs in a minority of people during the course of treatment.[49][50] A strategy involving the use of pharmacotherapy in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies.[51][52]

Antidepressants are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder of which the central feature is excessive worry about a number of different events. Key symptoms include excessive anxiety about multiple events and issues, and difficulty controlling worrisome thoughts that persists for at least 6 months.

Antidepressants provide a modest-to-moderate reduction in anxiety in GAD,[53] and are superior to placebo in treating GAD.[54] The efficacy of different antidepressants is similar.[53][54]

SSRIs are a second-line treatment of adult obsessive–compulsive disorder (OCD) with mild functional impairment and as first-line treatment for those with moderate or severe impairment. In children, SSRIs can be considered as a second-line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects.[55] SSRIs are efficacious in the treatment of OCD; patients treated with SSRIs are about twice as likely to respond to treatment as those treated with placebo.[56][57] Efficacy has been demonstrated both in short-term treatment trials of 6 to 24 weeks and in discontinuation trials of 28 to 52 weeks duration.[58][59][60]

Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa.[61] SSRIs (fluoxetine in particular) are preferred over other antidepressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized. Bupropion is not recommended for the treatment of eating disorders due to an increased risk of seizure.[62]

Similar recommendations apply to binge eating disorder.[61] SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.[63]

Clinical trials have generated mostly negative results for the use of SSRIs in the treatment of anorexia nervosa.[64] Treatment guidelines from the National Institute of Health and Care Excellence[61] recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association note that SSRIs confer no advantage regarding weight gain, but that they may be used for the treatment of co-existing depressive, anxiety, or obsessiveâ€“compulsive disorders.[63]

A 2012 meta-analysis concluded that antidepressants treatment favorably affects pain, health-related quality of life, depression, and sleep in fibromyalgia syndrome. Tricyclics appear to be the most effective class, with moderate effects on pain and sleep and small effects on fatigue and health-related quality of life. The fraction of people experiencing a 30% pain reduction on tricyclics was 48% versus 28% for placebo. For SSRIs and SNRIs the fraction of people experiencing a 30% pain reduction was 36% (20% in the placebo comparator arms) and 42% (32% in the corresponding placebo comparator arms). Discontinuation of treatment due to side effects was common.[65] Antidepressants including amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole are recommended by the European League Against Rheumatism (EULAR) for the treatment of fibromyalgia based on "limited evidence".[66]

A 2014 meta-analysis from the Cochrane Collaboration found the antidepressant duloxetine to be effective for the treatment of pain resulting from diabetic neuropathy.[67] The same group reviewed data for amitriptyline in the treatment of neuropathic pain and found limited useful randomized clinical trial data. They concluded that the long history of successful use in the community for the treatment of fibromyalgia and neuropathic pain justified its continued use.[68] The group was concerned about the potential for overestimating the amount of pain relief provided by amitriptyline, and highlighted that only a small number of people will experience significant pain relief by taking this medication.[68]

Antidepressants may be modestly helpful for treating people who both have depression and alcohol dependence, however the evidence supporting this association of low quality.[69]

Difficulty tolerating adverse effects is the most common reason for antidepressant discontinuation.[medical citation needed]

Almost any medication involved with serotonin regulation has the potential to cause serotonin toxicity (also known as serotonin syndrome) –  an excess of serotonin that can induce mania, restlessness, agitation, emotional lability, insomnia and confusion as its primary symptoms.[70][71] Although the condition is serious, it is not particularly common, generally only appearing at high doses or while on other medications. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal.[72][73]

MAOIs tend to have pronounced (sometimes fatal) interactions with a wide variety of medications and over-the-counter drugs. If taken with foods that contain very high levels of tyramine (e.g., mature cheese, cured meats, or yeast extracts), they may cause a potentially lethal hypertensive crisis. At lower doses the person may be bothered by only a headache due to an increase in blood pressure.[74]

In response to these adverse effects, a different type of MAOI has been developed: the reversible inhibitor of monoamine oxidase A (RIMA) class of drugs. Their primary advantage is that they do not require the person to follow a special diet, while being purportedly effective as SSRIs and tricyclics in treating depressive disorders.[75]

SSRI use in pregnancy has been associated with a variety of risks with varying degrees of proof of causation. As depression is independently associated with negative pregnancy outcomes, determining the extent to which observed associations between antidepressant use and specific adverse outcomes reflects a causative relationship has been difficult in some cases.[76] In other cases, the attribution of adverse outcomes to antidepressant exposure seems fairly clear.

SSRI use in pregnancy is associated with an increased risk of spontaneous abortion of about 1.7-fold,[77][78] and is associated with preterm birth and low birth weight.[79]

A systematic review of the risk of major birth defects in antidepressant-exposed pregnancies found a small increase (3% to 24%) in the risk of major malformations and a risk of cardiovascular birth defects that did not differ from non-exposed pregnancies.[80] A study of fluoxetine-exposed pregnancies found a 12% increase in the risk of major malformations that just missed statistical significance.[81] Other studies have found an increased risk of cardiovascular birth defects among depressed mothers not undergoing SSRI treatment, suggesting the possibility of ascertainment bias, e.g. that worried mothers may pursue more aggressive testing of their infants.[82] Another study found no increase in cardiovascular birth defects and a 27% increased risk of major malformations in SSRI exposed pregnancies.[78] The FDA advises for the risk of birth defects with the use of paroxetine[83] and the MAOI should be avoided.

A 2013 systematic review and meta-analysis found that antidepressant use during pregnancy was statistically significantly associated with some pregnancy outcomes, such as gestational age and preterm birth, but not with other outcomes. The same review cautioned that because differences between the exposed and unexposed groups were small, it was doubtful whether they were clinically significant.[84]

A neonate (infant less than 28Â days old) may experience a withdrawal syndrome from abrupt discontinuation of the antidepressant at birth. Antidepressants have been shown to be present in varying amounts in breast milk, but their effects on infants are currently unknown.[85]

Moreover, SSRIs inhibit nitric oxide synthesis, which plays an important role in setting vascular tone. Several studies have pointed to an increased risk of prematurity associated with SSRI use, and this association may be due to an increase risk of pre-eclampsia of pregnancy.[86]

Another possible problem with antidepressants is the chance of antidepressant-induced mania in patients with bipolar disorder. Many cases of bipolar depression are very similar to those of unipolar depression. Therefore, the patient can be misdiagnosed with unipolar depression and be given antidepressants. Studies have shown that antidepressant-induced mania can occur in 20â€“40% of bipolar patients.[87] For bipolar depression, antidepressants (most frequently SSRIs) can exacerbate or trigger symptoms of hypomania and mania.[88]

Studies have shown that the use of antidepressants is correlated with an increased risk of suicidal behaviour and thinking (suicidality) in those aged under 25.[89] This problem has been serious enough to warrant government intervention by the US Food and Drug Administration (FDA) to warn of the increased risk of suicidality during antidepressant treatment.[90] According to the FDA, the heightened risk of suicidality is within the first one to two months of treatment.[91][92] The National Institute for Health and Care Excellence (NICE) places the excess risk in the "early stages of treatment".[93] A meta-analysis suggests that the relationship between antidepressant use and suicidal behavior or thoughts is age-dependent.[89] Compared to placebo the use of antidepressants is associated with an increase in suicidal behavior or thoughts among those aged under 25 (OR=1.62). This increase in suicidality approaches that observed in children and adolescents. There is no effect or possibly a mild protective effect among those aged 25 to 64 (OR=0.79). Antidepressant treatment has a protective effect against suicidality among those aged 65 and over (OR=0.37).[89][94]

Sexual side-effects are also common with SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction.[95] Although usually reversible, these sexual side-effects can, in rare cases, last for months or years after the drug has been completely withdrawn.[96]

In a study of 1022 outpatients, overall sexual dysfunction with all antidepressants averaged 59.1%[97] with SSRIs values between 57 and 73%, mirtazapine 24%, nefazodone 8%, amineptine 7% and moclobemide 4%. Moclobemide, a selective reversible MAO-A inhibitor, does not cause sexual dysfunction,[98] and can actually lead to an improvement in all aspects of sexual function.[99]

Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting 5-HT2 and 5-HT3 receptors; decreased dopamine; decreased norepinephrine; blockade of cholinergic and Î±1adrenergic receptors; inhibition of nitric oxide synthetase; and elevation of prolactin levels.[100] Mirtazapine is reported to have fewer sexual side-effects, most likely because it antagonizes 5-HT2 and 5-HT3 receptors and may, in some cases, reverse sexual dysfunction induced by SSRIs by the same mechanism.[101]

Bupropion, a weak NDRI and nicotinic antagonist, may be useful in treating reduced libido as a result of SSRI treatment.[102]

Changes in appetite or weight are common among antidepressants, but largely drug-dependent and are related to which neurotransmitters they affect. Mirtazapine and paroxetine, for example, have the effect of weight gain and/or increased appetite,[103][104][105] while others (such as bupropion and venlafaxine) achieve the opposite effect.[106][107]

The antihistaminic properties of certain TCA- and TeCA-class antidepressants have been shown to contribute to the common side-effects of increased appetite and weight gain associated with these classes of medication.

Antidepressant discontinuation symptoms were first reported with imipramine, the first tricyclic antidepressant (TCA), in the late 1950s, and each new class of antidepressants has brought reports of similar conditions, including monoamine oxidase inhibitors (MAOIs), SSRIs, and SNRIs. As of 2001, at least 21 different antidepressants, covering all the major classes, were known to cause discontinuation syndromes.[108] The problem has been poorly studied, and most of the literature has been case reports or small clinical studies; incidence is hard to determine and controversial.[108]

People with discontinuation syndrome have been on an antidepressant for at least four weeks and have recently stopped taking the medication, either abruptly or after a fast taper.[109] Common symptoms include flu-like symptoms (nausea, vomiting, diarrhea, headaches, sweating), sleep disturbances (insomnia, nightmares, constant sleepiness), sensory/movement disturbances (imbalance, tremors, vertigo, dizziness, electric-shock-like experiences), mood disturbances (dysphoria, anxiety, agitation) and cognitive disturbances (confusion and hyperarousal).[109][110][111] Over fifty symptoms have been reported.[112]

Most cases of discontinuation syndrome last between one and four weeks, are relatively mild, and resolve on their own; in rare cases symptoms can be severe or extended.[109] Paroxetine and venlafaxine seem to be particularly difficult to discontinue and prolonged withdrawal syndrome lasting over 18 months have been reported with paroxetine.[108][113][114]

With the explosion of use and interest in SSRIs in the late 1980s and early 1990s, focused especially on Prozac, interest grew as well in discontinuation syndromes.[115] In the late 1990s, some investigators thought that symptoms that emerged when antidepressants were discontinued, might mean that antidepressants were causing addiction, and some used the term "withdrawal syndrome" to describe the symptoms. Addictive substances cause physiological dependence, so that drug withdrawal causes suffering. These theories were abandoned, since addiction leads to drug-seeking behavior, and people taking antidepressants do not exhibit drug-seeking behavior. The term "withdrawal syndrome" is no longer used with respect to antidepressants, to avoid confusion with problems that arise from addiction.[109][116][117] There are case reports of antidepressants being abused, but these are rare and are mostly limited to antidepressants with stimulant effects and to people who already had a substance use disorder.[118] A 2012 comparison of the effects of stopping therapy with benzodiazepines and SSRIs argued that because the symptoms are similar, it makes no sense to say that benzodiazepines are addictive while SSRIs are not.[119] Responses to that review noted that there is no evidence that people who stop taking SSRIs exhibit drug-seeking behavior while people who stop taking benzodiazepines do, and that the drug classes should be considered differently.[120][121]

Antidepressants can cause emotional blunting, or numbness. This is a reduction in extremes of emotion, both positive and negative. While the patient may feel less depressed, they may also feel less happiness or empathy in some situations. This may be cause for a dose reduction or medication change. The exact mechanism is unknown.[122][123]

The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis (which can be traced back to the 1950s), which states that depression is due to an imbalance (most often a deficiency) of the monoamine neurotransmitters (namely serotonin, norepinephrine and dopamine).[124] It was originally proposed based on the observation that certain hydrazine anti-tuberculosis agents produce antidepressant effects, which was later linked to their inhibitory effects on monoamine oxidase, the enzyme that catalyses the breakdown of the monoamine neurotransmitters.[124] All currently marketed antidepressants have the monoamine hypothesis as their theoretical basis, with the possible exception of agomelatine which acts on a dual melatonergic-serotonergic pathway.[124] Despite the success of the monoamine hypothesis it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, there are a sizeable portion (>40%) of depressed patients that do not adequately respond to monoaminergic antidepressants.[125][126] A number of alternative hypotheses have been proposed, including the glutamate, neurogenic, epigenetic, cortisol hypersecretion and inflammatory hypotheses.[125][126][127][128]

Selective serotonin reuptake inhibitors (SSRIs) are believed to increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the norepinephrine and dopamine transporters.

SSRIs are the most widely prescribed antidepressants in many countries.[129] The efficacy of SSRIs in mild or moderate cases of depression has been disputed.[18][130][131][132]

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are potent inhibitors of the reuptake of serotonin and norepinephrine. These neurotransmitters are known to play an important role in mood. SNRIs can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act mostly upon serotonin alone.

The human serotonin transporter (SERT) and norepinephrine transporter (NET) are membrane proteins that are responsible for the reuptake of serotonin and norepinephrine. Balanced dual inhibition of monoamine reuptake can possibly offer advantages over other antidepressants drugs by treating a wider range of symptoms.[133]

SNRIs are sometimes also used to treat anxiety disorders, obsessive–compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), chronic neuropathic pain, and fibromyalgia syndrome (FMS), and for the relief of menopausal symptoms.

Serotonin modulator and stimulators (SMSs), sometimes referred to more simply as serotonin modulators, are a type of drug with a multimodal action specific to the serotonin neurotransmitter system. To be precise, SMSs simultaneously modulate one or more serotonin receptors and inhibit the reuptake of serotonin. The term was created to describe the mechanism of action of the serotonergic antidepressant vortioxetine, which acts as a serotonin reuptake inhibitor (SRI), partial agonist of the 5-HT1A receptor, and antagonist of the 5-HT3 and 5-HT7 receptors.[134][135][136] However, it can also technically be applied to vilazodone, which is an antidepressant as well and acts as an SRI and 5-HT1A receptor partial agonist.[137]

An alternative term is serotonin partial agonist/reuptake inhibitor (SPARI), which can be applied only to vilazodone.[138]

Serotonin antagonist and reuptake inhibitors (SARIs) while mainly used as antidepressants, are also anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also act as Î±1-adrenergic receptor antagonists. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds. They include trazodone and nefazodone.

Norepinephrine reuptake inhibitors (NRIs or NERIs) are a type of drug that acts as a reuptake inhibitor for the neurotransmitter norepinephrine (noradrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine.

NRIs are commonly used in the treatment of conditions like ADHD and narcolepsy due to their psychostimulant effects and in obesity due to their appetite suppressant effects. They are also frequently used as antidepressants for the treatment of major depressive disorder, anxiety and panic disorder. Additionally, many drugs of abuse such as cocaine and methylphenidate possess NRI activity, though it is important to mention that NRIs without combined dopamine reuptake inhibitor (DRI) properties are not significantly rewarding and hence are considered to have a negligible abuse potential.[139][140] However, norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined (e.g., in the case of NDRIs) to produce rewarding effects in psychostimulant drugs of abuse.[141]

The majority of the tricyclic antidepressants (TCAs) act primarily as serotonin–norepinephrine reuptake inhibitors (SNRIs) by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), respectively, which results in an elevation of the synaptic concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission.[142][143] Notably, with the sole exception of amineptine, the TCAs have negligible affinity for the dopamine transporter (DAT), and therefore have no efficacy as dopamine reuptake inhibitors (DRIs).[142]

Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs.[144]

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their chemical structure, which contains four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression.[145] They are also used in the treatment of Parkinson's disease and several other disorders.

Because of potentially lethal dietary and drug interactions, monoamine oxidase inhibitors have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.[146]

MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia,[147] social phobia,[148][149][150] atypical depression[151][152] or mixed anxiety and depression, bulimia,[153][154][155][156] and post-traumatic stress disorder,[157] as well as borderline personality disorder.[158] MAOIs appear to be particularly effective in the management of bipolar depression according to a recent[when?] retrospective-analysis.[159] There are reports of MAOI efficacy in obsessive–compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports.[160]

MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety disorders.

See the list of antidepressants for other drugs which are not specifically characterized.

Adjunct medications are an umbrella term used to describe substances that increase the potency or "enhance" antidepressants.[161] They work by affecting variables very close to the antidepressant, sometimes affecting a completely different mechanism of action. This may be attempted when depression treatments have not been successful in the past.

Common types of adjunct medication techniques generally fall into the following categories:

It is unknown if undergoing psychological therapy at the same time as taking anti-depressants enhances the anti-depressive effect of the medication.[163]

Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone.[164] Furthermore, lithium dramatically decreases the suicide risk in recurrent depression.[165] There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function.[166]

Psychopharmacologists have also tried adding a stimulant, in particular, d-amphetamine.[167] However, the use of stimulants in cases of treatment-resistant depression is relatively controversial.[168][169] A review article published in 2007 found psychostimulants may be effective in treatment-resistant depression with concomitant antidepressant therapy, but a more certain conclusion could not be drawn due to substantial deficiencies in the studies available for consideration, and the somewhat contradictory nature of their results.[169]

Before the 1950s, opioids and amphetamines were commonly used as antidepressants.[170][171] Their use was later restricted due to their addictive nature and side effects.[170] Extracts from the herb St John's wort have been used as a "nerve tonic" to alleviate depression.[172]

In 1951, Irving Selikoff and Edward Robitzek, working out of Sea View Hospital on Staten Island, began clinical trials on two new anti-tuberculosis agents developed by Hoffman-LaRoche, isoniazid and iproniazid. Only patients with a poor prognosis were initially treated; nevertheless, their condition improved dramatically. Selikoff and Robitzek noted "a subtle general stimulation â€¦ the patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems."[173] The promise of a cure for tuberculosis in the Sea View Hospital trials was excitedly discussed in the mainstream press.

In 1952, learning of the stimulating side effects of isoniazid, the Cincinnati psychiatrist Max Lurie tried it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved depression in two thirds of their patients and coined the term antidepressant to describe its action.[174] A similar incident took place in Paris, where Jean Delay, head of psychiatry at Sainte-Anne Hospital, heard of this effect from his pulmonology colleagues at Cochin Hospital. In 1952 (before Lurie and Salzer), Delay, with the resident Jean-Francois Buisson, reported the positive effect of isoniazid on depressed patients.[175] The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of diamine oxidase, coupled with a weak inhibition of monoamine oxidase A.[176]

Selikoff and Robitzek also experimented with another anti-tuberculosis drug, iproniazid; it showed a greater psychostimulant effect, but more pronounced toxicity.[177] Later, Jackson Smith, Gordon Kamman, George Crane, and Frank Ayd, described the psychiatric applications of iproniazid. Ernst Zeller found iproniazid to be a potent monoamine oxidase inhibitor.[178] Nevertheless, iproniazid remained relatively obscure until Nathan Kline, the influential head of research at Rockland State Hospital, began to popularize it in the medical and popular press as a "psychic energizer".[178][179] Roche put a significant marketing effort behind iproniazid.[178] Its sales grew until it was recalled in 1961, due to reports of lethal hepatotoxicity.[178]

The antidepressant effect of a tricyclic, a three ringed compound, was first discovered in 1957 by Roland Kuhn in a Swiss psychiatric hospital. Antihistamine derivatives were used to treat surgical shock and later as neuroleptics. Although in 1955 reserpine was shown to be more effective than placebo in alleviating anxious depression, neuroleptics were being developed as sedatives and antipsychotics.[medical citation needed]

Attempting to improve the effectiveness of chlorpromazine, Kuhn –  in conjunction with the Geigy Pharmaceutical Company –  discovered the compound "G 22355", later renamed imipramine. Imipramine had a beneficial effect in patients with depression who showed mental and motor retardation. Kuhn described his new compound as a "thymoleptic" "taking hold of the emotions," in contrast with neuroleptics, "taking hold of the nerves" in 1955–56. These gradually became established, resulting in the patent and manufacture in the US in 1951 by Häfliger and SchinderA.[180]

Antidepressants became prescription drugs in the 1950s. It was estimated that no more than 50 to 100 individuals per million suffered from the kind of depression that these new drugs would treat, and pharmaceutical companies were not enthusiastic in marketing for this small market. Sales through the 1960s remained poor compared to the sales of tranquilizers,[181] which were being marketed for different uses.[182] Imipramine remained in common use and numerous successors were introduced. The use of monoamine oxidase inhibitors (MAOI) increased after the development and introduction of "reversible" forms affecting only the MAO-A subtype of inhibitors, making this drug safer to use.[182][183]

By the 1960s, it was thought that the mode of action of tricyclics was to inhibit norepinephrine reuptake. However, norepinephrine reuptake became associated with stimulating effects. Later tricyclics were thought to affect serotonin as proposed in 1969 by Carlsson and Lindqvist as well as Lapin and Oxenkrug.[medical citation needed]

Researchers began a process of rational drug design to isolate antihistamine-derived compounds that would selectively target these systems. The first such compound to be patented was zimelidine in 1971, while the first released clinically was indalpine. Fluoxetine was approved for commercial use by the US Food and Drug Administration (FDA) in 1988, becoming the first blockbuster SSRI. Fluoxetine was developed at Eli Lilly and Company in the early 1970s by Bryan Molloy, Klaus Schmiegel, David Wong and others.[184][185] SSRIs became known as "novel antidepressants" along with other newer drugs such as SNRIs and NRIs with various selective effects.[186]

St John's wort fell out of favor in most countries through the 19th and 20th centuries, except in Germany, where Hypericum extracts were eventually licensed, packaged and prescribed. Small-scale efficacy trials were carried out in the 1970s and 1980s, and attention grew in the 1990s following a meta-analysis.[187] It remains an over-the-counter drug (OTC) supplement in most countries. Research continues to investigate its active component hyperforin, and to further understand its mode of action.[188][189]

In the United States, antidepressants were the most commonly prescribed medication in 2013.[190] Of the estimated 16 million "long term" (over 24 months) users, roughly 70 percent are female.[190]

In the UK, figures reported in 2010 indicated that the number of antidepressant prescribed by the National Health Service (NHS) almost doubled over a decade.[191] Further analysis published in 2014 showed that number of antidepressants dispensed annually in the community went up by 25 million in the 14 years between 1998 and 2012, rising from 15 million to 40 million. Nearly 50% of this rise occurred in the four years after the 2008 banking crash, during which time the annual increase in prescriptions rose from 6.7% to 8.5%.[192] These sources also suggest that aside from the recession, other factors that may influence changes in prescribing rates may include: improvements in diagnosis, a reduction of the stigma surrounding mental health, broader prescribing trends, GP characteristics, geographical location and housing status. Another factor that may contribute to increasing consumption of antidepressants is the fact that these medications now are used for other conditions including social anxiety and post traumatic stress.

United States: The most commonly prescribed antidepressants in the US retail market in 2010 were:[193]

Netherlands: In the Netherlands, paroxetine, marketed as Seroxat among generic preparations, is the most prescribed antidepressant, followed by amitriptyline, citalopram and venlafaxine.[194]

As of 2003, worldwide, 30 to 60% of people didn't follow their practitioner's instructions about taking their antidepressants,[195] and as of 2013 in the US, it appeared that around 50% of people did not take their antidepressants as directed by their practitioner.[196]

When people fail to take their antidepressants, there is a greater risk that the drug won't help, that symptoms get worse, that they miss work or are less productive at work, and that the person may be hospitalized.[197] This also increases costs for caring for them.[197]

In looking at the issue of antidepressant use, some academics have highlighted the need to examine the use of antidepressants and other medical treatments in cross-cultural terms, due to the fact that various cultures prescribe and observe different manifestations, symptoms, meanings and associations of depression and other medical conditions within their populations.[198][199] These cross-cultural discrepancies, it has been argued, then have implications on the perceived efficacy and use of antidepressants and other strategies in the treatment of depression in these different cultures.[198][199] In India antidepressants are largely seen as tools to combat marginality, promising the individual the ability to re-integrate into society through their useâ€”a view and association not observed in the West.[198]

Because most antidepressants function by inhibiting the reuptake of neurotransmitters serotonin, dopamine, and norepinepherine[200] these drugs can interfere with natural neurotransmitter levels in other organisms impacted by indirect exposure.[201] Antidepressants fluoxetine and sertraline have been detected in aquatic organisms residing in effluent dominated streams.[202] The presence of antidepressants in surface waters and aquatic organisms has caused concern because ecotoxicological effects to aquatic organisms due to fluoxetine exposure have been demonstrated.[203]

Coral reef fish have been demonstrated to modulate aggressive behavior through serotonin.[204] Artificially increasing serotonin levels in crustaceans can temporarily reverse social status and turn subordinates into aggressive and territorial dominant males.[205]

Exposure to fluoxetine has been demonstrated to increase serotonergic activity in fish, subsequently reducing aggressive behavior.[206] Perinatal exposure to fluoxetine at relevant environmental concentrations has been shown to lead to significant modifications of memory processing in 1-month-old cuttlefish.[207] This impairment may disadvantage cuttlefish and decrease their survival. Somewhat less than 10% of orally administered fluoxetine is excreted from humans unchanged or as glucuronide.[208][209]


who enforces the canada labour code part ii and its regulations

Industrialization in Canada, as elsewhere, brought with it increasingly poor employment standards. Employers often took advantage of their workers by providing them with little to no health and safety elements in the workplace and no job security. When the workers formed unions, negotiations between the employer and union often dragged on or broke down completely. In these instances the unions would use techniques such as strikes and sabotage to impress on the employer the idea that the workers had rights as humans and even deserved respect. The unionism would then often build solidarity between workers, even in different industries. In response, the Canadian government established the Conciliation Act of 1900. This act created the federal Department of Labour whose purpose was to help settle labour disputes and promote fair wages and proper conditions for workers.

Canada Labour Code

The Canada Labour Code (French: Code canadien du travail) is an Act of Parliament of the Canadian government to consolidate certain statutes respecting labour. The objective of the code is to facilitate production by controlling strikes & lockouts, occupational safety and health, and some employment standards.

Generally speaking, the code only applies to those industries in which the federal government has jurisdiction instead of the provinces. These industries include: broadcasting, telecommunications, chartered banks, postal service, airports and air transportation, shipping and navigation, interprovincial or international transportation (i.e., road, railway, ferry or pipeline). It also applies to businesses in the Territories, on First Nations reserves, and certain crown corporations. It also applies to the Royal Canadian Mounted Police (RCMP)and the military, and those covered under the (now repealed) Public Service Staff Relations Act (RS 1985, c. P-35) or its successor Public Service Modernization Act (2003, c. 22).

The Department had little success but determined that they required the authority to impose conciliation amongst the union and employer. After the 1906 Lethbridge coalfield strike, this requirement became paramount and was introduced in the Industrial Disputes Investigation (IDI) Act of 1907. This act also introduced compulsory investigation of labour disputes, a prohibition of work stoppages pending this investigation, and the requirement for compromise. As the industries continued to resist the demands laid down by the unions, the organizations grew larger and began to plan large-scale tactics such as the Winnipeg General Strike. This created even more fear in the government concerning unions and led to further legislation.

During World War II, the wartime government suspended provincial labour legislation and the IDI act. However, the Wartime Labour Relations Regulations (Order in Council P.C. 1003) of 1944 introduced the provisions for certification of unions, leading to the temporary dissolution and outlawing of the major solidarity unions in Canada (including the IWW and the One Big Union). The WLRR also introduced the duty to meet and bargain in good faith, prohibitions of unfair labour practices, and the introduction of a labour relations board.

In 1948, this Order in Council and the IDI act were consolidated into the Industrial Relations and Disputes Investigation Act. In 1967, this act was consolidated, along with other statutes, as Part V of the Canada Labour Code, (S.C. 1966-67, c. 62).

Significant amendments were made to this part of the code in 1973. These amendments included extending bargaining rights to some previously excluded groups (e.g., supervisors, employed professionals, etc.) and expanding the jurisdiction of the labour relations board to include enforcement and remedial powers. Also, provisions for adjustments to technological changes were introduced. Finally, in 1988 the Code was reissued as part of the Revised Statutes of Canada, (R.S.C. 1985, c. L-2.), wherein Part V became Part I.

The Act is divided into three distinct parts. The first part deals with collective bargaining between unions and employers. It comes mostly from the Industrial Relations and Disputes Investigation Act of 1948. The second part deals with health & safety in the workplace. The third part deals with employment standards but defers mostly to Provincial legislation for each province of employment.

This part of the act is divided into seven divisions and deals with collective bargaining, dispute resolution, strikes and lockouts. It, first of all, establishes basic freedoms, in accordance with Convention C87 of the International Labour Organization, by setting out that employees are “free to join the trade union of their choice and to participate in its lawful activities” [s.8(1)] and employers, likewise, are free to organize.

Divisions III, IV, V.1, and VI, set out the procedures and regulations for collective bargaining. In short, a trade union for employees or an organization representing employers must first be certified by the Canada Labour Relations Board, whose composition and procedures are detailed in Division II. The act places a duty on the two sides to meet and negotiate “in good faith and make every reasonable effort to enter into a collective agreement” [s.50 (a) i,ii].

The role of the Canada Labour Relations Board is to interpret the code and to investigate allegations of unfair labour practices and failures to bargain in good faith. Division V details the role of the Federal Mediation and Conciliation Service. It is “responsible for fostering harmonious relations between trade unions and employers by assisting them in the negotiation of collective agreements and their renewal.” [s.70.1(1)] They are employees of the Human Resources Development Canada and report to the Minister of Labour.

Divisions V.1 and VI set out conditions for strikes and lockouts. Before such work stoppages occur a secret ballot vote must result in a majority wishing to proceed with a work stoppage. However, this cannot occur during the term of an agreement, only once it expires. The union (for strikes) or the employers (for lockouts) must give the Minister of Labour 72 hours' notice before the work stoppage can occur. The Minister can prevent or cease a work stoppage by appointing a conciliation officer, commissioner, or board, to mediate negotiations. Section 100 of the Code sets a limit of $1000 per day is set for illegal lockouts or strikes.

Also of note, Division IV sets out special arrangements for interruptions in employment due to technological change. It also allows union dues to be deducted from an employers wages, and, in case of religious objections, forward the amount deducted to a registered charity mutually agreed on by the employee and the trade union. Division V.1 prohibits work stoppages “to the extent necessary to prevent an immediate and serious danger to the safety or health of the public.” [s.87.4(1)]

This part of the act deals with maintaining the health and safety of workers in the workplace. It focuses on the recognition and prevention of hazards. The beginning of this part states the purpose here “is to prevent accidents and injury to health arising out of, linked with or occurring in the course of employment.” [s.122.1]

Sections 124 and 125 set out the duties of employers with regard to the health and safety of their employees. A list is provided of 45 general and specific duties for the employer to follow. For example, these duties include providing first-aid facilities, potable water, sanitary and personal facilities (i.e., washrooms), prescribed safety materials, equipment, devices and clothing, safety manuals in telecommunications companies and other industries and so on. These duties extend beyond the workplace and include all areas in which an employee may travel in the course of a work day. The employers are also responsible for third party contractors and any other people with whom they are in an employment relationship. Sections 122.3 and 132 establish conditions for employees with a special needs and pregnant and nursing employees.

Section 126 sets out the duties of employees. It is their duty to “take all reasonable and necessary precautions to ensure the health and safety of the employee, the other employees and any person likely to be affected by the employee's acts or omissions” [s.126(1)(c)] and to use any safety features that the employer provides.

In cases of conflict between the employee and employer sections 127.1 and 128 set out a resolution process. An employee is permitted to â€œrefuse to use or operate a machine or thing, to work in a place or to perform an activity, if the employee while at work has reasonable cause to believe that the performance of the activity constitutes a danger to the employee or to another employee." [s.128 (1)(c)] All complaints must be reasonably investigated to find if the claim is justified.

In order to facilitate investigations sections 134 to 140 establish requirements, regulations, and procedures for health and safety committees, representatives, and officers. For workplaces with 20 or more employees a committee must be established consisting of at least two employees. For workplaces with fewer than 20 employees at least one representative must be selected by the non-managerial employee as a Health and Safety Representative. The employer must be readily accessible to this representative in order to address health and safety matters. Regional Health and Safety Officers are appointed by the Minister of Labour and investigate incidents and complaints concerning health and safety in the workplace. Violations for this part of the Labour Code can be punishable by up to two years in jail and a $1,000,000 fine as set out in section 148. A death or injury that resulted in combination with a violation of this part of the act can be viewed as a criminal act and prosecuted as such.

It should also be noted that special conditions are set out for coal mines. Section 137.1 establishes the composition, procedures and regulations of a Coal Mining Safety Commission. Section 125.3 requires employers to submit their plans and procedures to this commission.

The third part of the code is divided into 16 divisions which deal with terms and conditions of employment concerning hours, wages, leave, holidays, and sexual harassment. It also sets the conditions for the termination of employment.

Division I establishes the eight-hour day and forty hour week but permits averaging if the profession demands extended hours. Workers must get at least one full day, “Sunday shall be the normal day of rest,” [s.173] and overtime is paid at least one and one-half times the normal wage. Division II establishes that the Province of employment’s minimum wage, with the exception of those based on age discrimination, shall be used for workers in industries under federal jurisdiction. This division also deals with wage deduction with respect to room, board, uniforms, tools, etc. Division III refers to the Canadian Human Rights Act for prohibition to discriminatory wage practices. These first three divisions should also be read with the Fair Wages and Hours of Labour Act (R.S. 1985, c. L-4 ) which concerns public works and those on government contracts. Also, division XV requires that payment of wages must be made within thirty days.

Divisions IV and V establish the amount, length and pay for vacations and holidays. Division VI allows the Governor in Council to make special regulations for industries that use multiple employers for the same job.

Divisions VII, VIII, XIII, and XIII.1 make arrangements for maternity, parental, compassionate care, bereavement, and sick leave. These sections say that “no employer shall dismiss, suspend, lay off, demote or discipline an employee because of absence due to illness or injury…”[s.239(1)], or any other of these aforementioned leave periods and that “pension, health and disability benefits and the seniority of any employee…[during] a leave of absence…shall accumulate during the entire period of the leave.”[s209.2(1)] Specifically, an employee is permitted 17 weeks of maternity leave, 37 weeks for parental leave, 8 weeks for compassionate care leave, and 3 days for bereavement leave. The leave period, and its associated benefits, due to illness or injury, depends upon the nature of the illness or injury and the period of absence.

Divisions IX to XII, XIV set the procedures for termination of employees. Division IX deals with lay-offs of 50 or more people wherein a 16-week notice must be given to the Minister of Human Resources and Skills Development and the Canada Employment Insurance Commission and a 2-week notice to individual employees. Division X deals with the termination of fewer than 50 people wherein 2 weeks' notice or 2 weeks' pay in lieu of notice must be given to the employee. Division XI deals with the allotment of severance pay and division XII prohibits termination or any other disciplinary action due to any garnishment proceedings of any employee. Division XIV makes provisions in cases of unjust dismissals. A complaint of an unjust dismissal may be made to an inspector who in turn can require the employer to provide a written statement of the reasons for the dismissal. If the inspector cannot settle the dispute then the Minister may appoint an adjudicator to resolve the dispute.

Division XV.1 prohibits sexual harassment by saying that “every employee is entitled to employment free of sexual harassment.” [s.247.2]. It defines sexual harassment as “any conduct, comment, gesture or contact of a sexual nature (a) that is likely to cause offence or humiliation to any employee; or (b) that might, on reasonable grounds, be perceived by that employee as placing a condition of a sexual nature on employment or on any opportunity for training or promotion.” [s.247.1]


the jimi hendrix experience axis bold as love

Axis: Bold as Love was first released in the United Kingdom by Track Records in December 1967, as the follow-up to the band's successful debut Are You Experienced, which had been released months earlier in May. It was not sold in the United States until 1968 because of the record company's fears that it might disturb the sales of the first album. Axis: Bold as Love charted at number five in the UK and number three in the US. The album also peaked at #6 on the Billboard R&B chart.[1]

Axis: Bold as Love

Axis: Bold as Love is the second studio album by English-American rock band the Jimi Hendrix Experience. It was recorded to fulfill the Experience's contract, which stated that they had to produce two records in 1967.

Following the completion of Are You Experienced at the end of April, 1967, the Jimi Hendrix Experience continued their schedule of regular recording sessions, returning to Olympic Studios in London on May 4, to begin composing material for a follow-up LP.[2] With Chas Chandler as producer, Eddie Kramer as engineer, and George Chkiantz as second engineer, the band started the session by working on a Noel Redding original that he had written about hippies titled, "She's So Fine". It featured back-ground vocals that were performed by Jimi Hendrix and Mitch Mitchell; Redding later recalled that Hendrix was enthusiastic to record the song because it was written in A with an open G chord that he enjoyed playing.[3] They achieved a working master on the 23rd take, over which Redding overdubbed his lead vocal.[3][nb 1] The band also made initial recordings of what would become "If 6 Was 9", using the working titles of "Section A" and "Section B" to identify its two distinct segments.[3] During a session that took place the following day, Hendrix and Mitchell improved "Section B", now titled "Symphony of Experience", by re-recording most of their guitar and drum parts. A reduction mix prepared by Kramer made room for additional overdubs, including Hendrix's lead vocal, backing vocals, and a percussion effect created by Chandler, Hendrix, and guests Graham Nash and Gary Leeds stomping their feet on a drum platform. As an additional oddity, Hendrix played a recorder on the track, achieving what they considered a satisfactory sound despite his complete lack of formal training with the instrument.[5][nb 2] Also recorded during these sessions was the experimental track "EXP".[7] In the span of two days, the group recorded basic tracks for seven compositions, though only three of them were included on the album.[7]

On May 9, the Experience reconvened at Olympic with Chandler, Kramer, and Chkiantz. Hendrix had been curious about a harpsichord that was stored in the facility's Studio A, so on this day he sat at the instrument and began writing "The Burning of the Midnight Lamp", a song that became the fourth UK single for the Experience. Hendrix attempted four takes before stopping for the day, producing a rough demo that was approximately a minute and a half in length.[5] On May 10, the band performed their latest single, "The Wind Cries Mary", on the BBC television program Top of the Pops.[9]

After a month-long break from the studio while they played gigs in Europe, the Experience returned to Olympic on Jun 5.[10] They devoted the session to a new Hendrix song titled "Cat Talking to Me", recording 17 takes before deciding that the second was the superior version, to which they added guitar and percussion overdubs after Kramer prepared a reduction mix. Although the song showed promise, no further work was completed on the track, which remains unreleased.[10]

On June 18, 1967, the Experience made their US debut at the Monterey Pop Festival.[11] Immediately after the festival, Bill Graham booked them for a series of five concerts at the Fillmore.[12][nb 3] While they were in California, Chandler booked session time for June 28, 29, and 30th at Houston Studios in Los Angeles. Although they worked on "Burning of the Midnight Lamp" and a new Hendrix composition, "The Stars That Play with Laughing Sam's Dice", they abandoned the inferior recordings. Chandler commented: "I booked three days there because I was told it was a state-of-the-art studio, but it was dire. The place was like a rehearsal studio compared to Olympic. Los Angeles was so far behind at that time."[14] After a week of performances in Los Angeles and New York, time was booked at Mayfair Studios for July 6 and 7.[15]

Axis: Bold As Love's scheduled release date was almost delayed when Hendrix lost the master tape of side one of the LP, leaving it in the back seat of a London taxi.[16] With the deadline looming, Hendrix, Chas Chandler, and engineer Eddie Kramer remixed most of side one in a single overnight session, but they could not match the quality of the lost mix of "If 6 Was 9". Bassist Noel Redding had a tape recording of this mix, which had to be smoothed out with an iron as it had gotten wrinkled.[17] During the verses, Hendrix doubled his singing with a guitar line which he played one octave lower than his vocals.[18] Hendrix voiced his disappointment about having re-mixed the album so quickly, and he felt that it could have been better had they been given more time.[16]

Although Kramer was always patient with Hendrix, who often demanded numerous re-takes, by October 1967, Chandler had grown weary of the guitarist's perfectionism.[19] Noel Redding was also frustrated by Hendrix's repeated demands for re-takes, and he began to resent Hendrix's explicit instructions regarding what he played in the studio.[20] Hendrix and Mitchell had begun to express their opinions regarding creative choices that had been left up to Chandler during the recording of Are You Experienced.[21] Mitchell commented: "Axis was the first time that it became apparent that Jimi was pretty good working behind the mixing board, as well as playing, and had some positive ideas of how he wanted things recorded. It could have been the start of any potential conflict between him and Chas in the studio."[22]

Many of the songs on Axis: Bold as Love were composed with studio recording techniques in mind and as a result were rarely performed live. Only "Spanish Castle Magic" and "Little Wing" were performed regularly. The lyrics of "Spanish Castle Magic" were inspired by The Spanish Castle, a dance hall in what is now Des Moines, Washington near Seattle where Hendrix jammed with local rock groups during his high school years. On "Little Wing" Hendrix plays his guitar through a Leslie speaker for the first time (a revolving speaker which creates a wavering effect, that is typically used with electric organs). According to Colin Larkin, Axis focused less on guitar playing than the previous Experience album, and more on Hendrix's "gifts as a songwriter".[23] Author Charles Shaar Murray described Axis as "lighter, looser and more melodic" than its predecessor.[24]

Axis: Bold as Love, opens with the track "EXP", which innovatively utilized microphonic and harmonic feedback.[25] It also showcased an experimental stereo panning effect in which sounds emanating from Hendrix's guitar move through the stereo image, revolving around the listener.[26] The piece reflected his growing interest in science fiction and outer space.[27] Author Keith Shadwick described the track as "some of the wildest music Hendrix ever released."[7]

"Wait Until Tomorrow" is a pop song with an R&B guitar riff with Mitchell and Redding singing backing vocals. The fifth track, "Ain't No Telling", is a rock song with a complex structure despite its short length. "Little Wing", as Hendrix himself said, was his impression of the Monterey Pop Festival put into the form of a girl.[28] "If 6 Was 9", the last song on side one, is the album's longest track and arguably the most psychedelic; Gary Leeds (from The Walker Brothers) and Graham Nash use their feet during the outro to make some stomping. The song features prominently on the soundtrack for the 1969 counterculture film, Easy Rider.

"You Got Me Floatin'", a rock song opening with a swirling backwards guitar solo (which is absent on the mysterious, differently mixed Polydor version of this LP [only available in stereo], which outside France and the UK was the only one available in Europe), opens the second side of the album. Roy Wood and Trevor Burton from The Move, who toured with Hendrix on a package tour through Britain during winter 1967, supplied backing vocals. The following track, "Castles Made of Sand", is a ballad also making use of a backwards guitar solo. "She's So Fine", Redding's contribution to the album as a composer, a very British pop/rock Who-influenced affair features Redding on lead vocals with help from Mitchell. "One Rainy Wish" begins as a ballad but develops a rock feel during the chorus that is in a different time signature than the verses.

The song "Little Miss Lover" was the first to feature a percussive muted wah-wah effect (with the fretboard hand "killing" notes) - a technique that was later adopted by many guitarists. The final song of the album, "Bold as Love", opens very abruptly. With a psychedelic chorus and an extended solo at the end it fades out the album. An early Mellotron instrument can be heard in the outro to the title track as well. In 2005, Rolling Stone ranked "Little Wing" number 366 in their list of the 500 Greatest Songs of All Time.[29]

Hendrix composed the album's title track and finale around two verses and two choruses, during which he pairs emotions with personas, comparing them to colors.[30] The song's coda features the first recording of stereo phasing.[31][nb 4] Numerous attempts at a basic rhythm track were undertaken before a satisfactory one was achieved on the 27th take.[33] Shadwick described the composition as "possibly the most ambitious piece on Axis, the extravagant metaphors of the lyrics suggesting a growing confidence" in Hendrix's songwriting.[34] His guitar playing throughout the song is marked by chordal arpeggios and contrapuntal motion, with tremolo-picked partial chords providing the musical foundation for the chorus, which culminates in what musicologist Andy Aledort described as "simply one of the greatest electric guitar solos ever played".[35] The track fades out on tremolo-picked thirty-second note double stops.[36] In 2011, Guitar World ranked the track number 24 in a list of Hendrix's 100 greatest performances.[33]

Hendrix expressed dismay regarding the album cover art, which depicts him and the Experience as various forms of Vishnu, incorporating a painting of them by Roger Law, from a photo-portrait by Karl Ferris.[37] Hendrix stated that the cover would have been more appropriate had it highlighted his American Indian heritage.[38] The painted image of the Experience was then superimposed on top of a copy of a mass-produced religious poster.[39] Hendrix commented: "The three of us have nothing to do with what's on the Axis cover."[40] Unlike the previous album's cover art, both the UK and US editions featured the same image.[41] Hindus have since expressed anger on the appropriation of the deity Vishnu for the album cover and poster. The Malaysian government's Home Ministry instituted a ban on the artwork from June 2014 to protect religious sensitivities following complaints.[42]

In November, a giant black and white blow-up of the Hapshash/Osiris poster featuring Hendrix dressed as a Native American wearing a feathered War Bonnet, was used as a background to his appearance on Hoepla, a controversial Dutch TV show. The original poster featured fantastic day-glo pink, orange & blue offset lithographs printed on gold foil. This poster, although produced later in London and supposedly commissioned by Hendrix, had text along the top to make it appear as if it was an original poster advertising his 1967 Fillmore concerts. The original prints of this poster are presumed to all be in private collections, and later copies which have surfaced have fetched high prices at auction.

The original Track UK issue came in a gatefold sleeve with a large black and white portrait photo of the group by Donald Silverstein spread over the inside and an orange sheet insert with overprinted lyrics in red; the allegedly high cost of this packaging was a topic of note in the music press. The US issue had no insert and instead of the group photo inside, had the lyrics. In Europe, the Polydor issue had no lyrics but added a 1-inch-wide (25Â mm) white border round the inside portrait, while the French dispensed with the original cover entirely and instead used a non-gatefold sleeve with a photo of the group taken from a recent French TV show on the front.

Track released Axis: Bold as Love in the UK on December 1, 1967, where it peaked at number five and spent 16 weeks on the charts.[52] In February 1968, it charted at number three in the United States.[53] The album was also well received by music critics, who praised its mixture of hard rock, rhythm and blues, and jazz.[54]

In a contemporary review for Rolling Stone, Jim Miller hailed Axis: Bold as Love as "the refinement of white noise into psychedelia... the finest voodoo album that any rock group has produced to date".[55] Q magazine wrote in a retrospective review that the album "dazzles as the Experience creates a genre probably short-lived because nobody else could play it".[49] AllMusic's Cub Koda considered it a demonstration of Hendrix's "remarkable growth and depth" as a songwriter, utilizing Curtis Mayfield-like soul guitar work, "Dylanesque lyrical imagery, and Fuzz Face hyperactivity to produce yet another side to his grand psychedelic musical vision".[43] According to author Peter Doggett, the record "heralded a new subtlety in Hendrix's work",[56] while BBC Music's Chris Jones said it is distinguished from his other Hendrix albums as his "coming-of-age-in-songwriting album... his peak in crafting pop rock perfection".[57]

Critics also found Axis: Bold as Love to be the least memorable of the Experience's three studio releases.[58] According to Richie Unterberger, it was the least impressive from the Experience,[59] while Kris Needs called the record a "transitional, but often overlooked, masterpiece".[60] In a mixed review for Blender, music essayist Robert Christgau acknowledged the adequate production and guitar quality on the album, but cautioned listeners of Mitchell's drumming, the music's "spaced-out lightness", and the short tracks: "half the songs are forgettable as songs if fine as recordings."[44]

In 2005, Rolling Stone ranked Axis: Bold as Love number 82 on their list of the 500 greatest albums of all time,[61] and the top spot on their list of the 40 greatest stoner albums in 2013. Guitarist magazine named the album number 7 on their list of "the most influential guitar albums of all time".[62] In 2015, Consequence of Sound described the album as "a compelling psychedelic masterpiece."[63] The album was also included in the book 1001 Albums You Must Hear Before You Die.[64]

All tracks written by Jimi Hendrix, except where noted.

The last recording by Hendrix to have a dedicated mono mix, which was only released in the UK and US. The album was released in stereo in the rest of the world. The Polydor (Europe and Japan only) release mysteriously had a different stereo mix from that originally released in the UK, France, the US and the rest of the world. It later appeared on a Backtrack budget LP release but before long replaced the original mix on all Polydor reissues and re-pressings, outside of French Barclay territory and US/Canada Reprise, including the first UK CD. This may have been a simple confusion over which tape in Polydor's library was sent to the mastering facility. Later CD reissues have reverted to the original mix. The 'Backtrack' mix can be found on Polydor CD 813 572-2, manufactured in West Germany.

The Jimi Hendrix Experience


what is the thirteenth letter in the alphabet

M (named em /ɛm/)[1] is the thirteenth letter of the modern English alphabet and the ISO basic Latin alphabet.

M

The letter M is derived from the Phoenician Mem, via the Greek Mu (Μ, μ). Semitic Mem is most likely derived from a "Proto-Sinaitic" (Bronze Age) adoption of the "water" ideogram in Egyptian writing. The Egyptian sign had the acrophonic value /n/, from the Egyptian word for "water", nt; the adoption as the Semitic letter for /m/ was presumably also on acrophonic grounds, from the Semitic word for "water", *mā(y)-.[2]

The letter ⟨m⟩ represents the bilabial nasal consonant sound [m] in the orthography of Latin as well as in that of many modern languages, and also in the International Phonetic Alphabet. In English, the Oxford English Dictionary (first edition) says that ⟨m⟩ is sometimes a vowel in words like spasm and in the suffix -ism. In modern terminology, this is described as a syllabic consonant (IPA [m̩]).

The Roman numeral â…¯ represents the number 1000, though it was not used in Roman times. There is, however, scant evidence that the letter was later introduced in the early centuries by the Romans. [3]


when did peter pan win the melbourne cup

Peter Pan was famous for winning the Melbourne Cup twice, in 1932 and 1934. In the running of the 1932 Melbourne Cup, Peter Pan, carrying Billy Duncan, was travelling at the rear of the pack when he clipped the heels of the horse in front and fell to his knees. Running behind him was his stablemate Dennis Boy, who bumped the champion back onto his feet. From there, Peter Pan raced past the pack to take out the race by a neck. When he was led into the winner's circle, a grass stain was clearly visible on his face. In 1933, Peter Pan fought a near-fatal viral disease that swept Sydney's racing stables and did not contest the Melbourne Cup. Frank McGrath Snr. personally nursed the horse back to health. Peter Pan won his 1934 Melbourne Cup carrying Darby Munro at 9 st 10 lb on his back and from an outside draw on a heavy track, hence his long odds of 14/1. In 1932, he also won the VRC Derby and the MacKinnon Stakes.

Peter Pan (Australian horse)

Peter Pan (1929â€“1941) was a chestnut Australian Thoroughbred racehorse and stallion.

Peter Pan was sired by Pantheon (GB) out of Alwina by St Alwyne (GB). He was foaled at the Baroona Stud north of Sydney Australia in 1929. His sire, Pantheon was an outstanding racehorse winning 10 races from 44 starts in England and Australia. Alwina did not race, but was a good broodmare.[2]

Peter Pan was known for having an unusual colouring for a Thoroughbred. He was chestnut with a blonde mane and tail. Frank McGrath's wife loved Peter Pan for his colouring and racing beauty.

Conditioned by future Hall of Fame trainer Frank McGrath, Sr., Peter Pan raced early in the 1930s during the Great Depression and with Phar Lap, Chatham and Rogilla, all household names at the time. Frank McGrath, Sr. and some others considered Peter Pan to possibly be a better horse than Phar Lap.

To win two Melbourne Cups is a rare feat, and this with his fine record gained him a place in the Australian Racing Hall of Fame. In 1935, Peter Pan suffered a recurrence of the illness that nearly killed him in 1933. Once again, Frank McGrath Snr. nursed him back to health but the horse was not his old self. Out of loyalty to the enormous public following that Peter Pan had gained, Rodney R. Dangar and McGrath agreed to start Peter Pan in the 1935 Melbourne Cup. The horse carried 10 st 5 lb (the weight carried by Carbine to win the 1890 Melbourne Cup) but finished 13th. He was immediately retired to stud.

1934 VRC Melbourne Cup racebook with train & turnstile passes.

Conditions & Starters showing the winner, Peter Pan.

1934 VRC Melbourne Cup racebook.

1934 VRC Melbourne Cup racebook.

The back cover showing raceday Railway Arrangements.

Peter Pan stood at Rodney R. Dangar's country property Baroona, Whittingham, Singleton, New South Wales where he exclusively covered his owner's mares. His stud career was cut short when he broke his leg in 1941 and was destroyed. Peter Pan is buried at Baroona, Whittingham, Singleton, New South Wales.[3]

Peter Pan sired the stakeswinners Grampian, Peter and Precept, who won the Moonee Valley Stakes and VRC Derby. Peter won the Williamstown Cup and placed 2nd in the 1944 Melbourne Cup.[2]

In 1978 he was honoured on a postage stamp issued by Australia Post [1].


early settled communities like catalhoyuk produced food by

Estonian folklorist Uku Masing has suggested as early as in 1976, that Çatalhöyük was probably a hunting and gathering religion and the Mother Goddess figurine did not represent a female deity. He implied that perhaps a longer period of time was needed in order to develop symbols for agricultural rites.[31] His theory was developed in the paper "Some remarks on the mythology of the people of Catal Hüyük".[32]

Çatalhöyük

Çatalhöyük (Turkish pronunciation: [tʃaˈtaɫhøjyk]; also Çatal Höyük and Çatal Hüyük; from Turkish çatal "fork" + höyük "mound") was a very large Neolithic and Chalcolithic proto-city settlement in southern Anatolia, which existed from approximately 7500 BC to 5700 BC, and flourished around 7000 BC.[1] In July 2012, it was inscribed as a UNESCO World Heritage Site.[2]

Çatalhöyük is located overlooking the Konya Plain, southeast of the present-day city of Konya (ancient Iconium) in Turkey, approximately 140 km (87 mi) from the twin-coned volcano of Mount Hasan. The eastern settlement forms a mound which would have risen about 20 m (66 ft) above the plain at the time of the latest Neolithic occupation. There is also a smaller settlement mound to the west and a Byzantine settlement a few hundred meters to the east. The prehistoric mound settlements were abandoned before the Bronze Age. A channel of the Çarşamba river once flowed between the two mounds, and the settlement was built on alluvial clay which may have been favourable for early agriculture.

The site was first excavated by James Mellaart in 1958. He later led a team which excavated there for four seasons between 1961 and 1965.[3][4][5][6] These excavations revealed this section of Anatolia as a centre of advanced culture in the Neolithic period.[7] Excavation revealed 18 successive layers of buildings signifying various stages of the settlement and eras of history. The bottom layer of buildings signifies as early as 7500 BC while the top layer is of 5600 BC.[8]

Mellaart was banned from Turkey for his involvement in the Dorak affair in which he published drawings of supposedly important Bronze Age artifacts that later went missing.[9] After this scandal, the site lay idle until 1993, when investigations began under the leadership of Ian Hodder, then at the University of Cambridge.[10][11][12][13] These investigations are among the most ambitious excavation projects currently in progress according to, among others, Colin Renfrew, Baron Renfrew of Kaimsthorn. In addition to extensive use of archaeological science, psychological and artistic interpretations of the symbolism of the wall paintings have been employed. Hodder, a former student of Mellaart, chose the site as the first "real world" test of his then-controversial theory of post-processual archaeology.[14]

Çatalhöyük was composed entirely of domestic buildings, with no obvious public buildings. While some of the larger ones have rather ornate murals, the purpose of some rooms remains unclear.[7]

The population of the eastern mound has been estimated to be, at maximum, 10,000 people, but the population likely varied over the communityâ€™s history. An average population of between 5,000 and 7,000 is a reasonable estimate. The sites were set up as large numbers of buildings clustered together. Households looked to their neighbors for help, trade, and possible marriage for their children.[15] The inhabitants lived in mudbrick houses that were crammed together in an aggregate structure. No footpaths or streets were used between the dwellings, which were clustered in a honeycomb-like maze. Most were accessed by holes in the ceiling, with doors reached by ladders and stairs. The rooftops were effectively streets. The ceiling openings also served as the only source of ventilation, allowing smoke from the houses' open hearths and ovens to escape.

farming, animal husbandry
pottery, metallurgy, wheel
circular ditches, henges, megaliths
Neolithic religion

Houses had plaster interiors characterized by squared-off timber ladders or steep stairs. These were usually on the south wall of the room, as were cooking hearths and ovens. The main rooms contained raised platforms that may have been used for a range of domestic activities. Typical houses contained two rooms for everyday activity, such as cooking and crafting.[15] All interior walls and platforms were plastered to a smooth finish.[7] Ancillary rooms were used as storage, and were accessed through low openings from main rooms.

All rooms were kept scrupulously clean. Archaeologists identified very little rubbish in the buildings, finding middens outside the ruins, with sewage and food waste, as well as significant amounts of wood ash. In good weather, many daily activities may also have taken place on the rooftops, which may have formed a plaza. In later periods, large communal ovens appear to have been built on these rooftops. Over time, houses were renewed by partial demolition and rebuilding on a foundation of rubble, which was how the mound was gradually built up. As many as eighteen levels of settlement have been uncovered.

As a part of ritual life, the people of Çatalhöyük buried their dead within the village.[15] Human remains have been found in pits beneath the floors and, especially, beneath hearths, the platforms within the main rooms, and under beds. Bodies were tightly flexed before burial and were often placed in baskets or wound and wrapped in reed mats. Disarticulated bones in some graves suggest that bodies may have been exposed in the open air for a time before the bones were gathered and buried. In some cases, graves were disturbed, and the individual’s head removed from the skeleton. These heads may have been used in rituals, as some were found in other areas of the community. In a woman's grave spinning whorls were recovered and in a man's grave, stone axes.[15] Some skulls were plastered and painted with ochre to recreate faces, a custom more characteristic of Neolithic sites in Syria and at Neolithic Jericho than at sites closer by.

Vivid murals and figurines are found throughout the settlement, on interior and exterior walls. Distinctive clay figurines of women, notably the Seated Woman of Çatalhöyük, have been found in the upper levels of the site.[16] Although no identifiable temples have been found, the graves, murals, and figurines suggest that the people of Çatalhöyük had a religion rich in symbols. Rooms with concentrations of these items may have been shrines or public meeting areas. Predominant images include men with erect phalluses, hunting scenes, red images of the now extinct aurochs (wild cattle) and stags, and vultures swooping down on headless figures.[7] Relief figures are carved on walls, such as of lionesses facing one another.

Heads of animals, especially of cattle, were mounted on walls. A painting of the village, with the twin mountain peaks of Hasan DaÄŸ in the background,[17] is frequently cited as the world's oldest map [18] and the first landscape painting.[7] However, some archaeologists question this interpretation. Stephanie Meece, for example, argues that it is more likely a painting of a leopard skin instead of a volcano, and a decorative geometric design instead of a map.[19]

Çatalhöyük had no apparent social classes, as no houses with distinctive features (belonging to royalty or religious hierarchy, for example) have been found so far. The most recent investigations also reveal little social distinction based on gender, with men and women receiving equivalent nutrition and seeming to have equal social status, as typically found in Paleolithic cultures.[20][21][22] Children observed domestic areas. They learned how to perform rituals and how to build or repair houses by watching the adults make statues, beads and other objects.[15] Çatalhöyük's spatial layout may be due to the close kin relations exhibited amongst the people. It can be seen, in the layout, that the people were "divided into two groups who lived on opposite sides of the town, separated by a gully." Furthermore, because no nearby towns were found from which marriage partners could be drawn, "this spatial separation must have marked two intermarrying kinship groups." This would help explain how a settlement so early on would become so large.[23]

In upper levels of the site, it becomes apparent that the people of Çatalhöyük were gaining skills in agriculture and the domestication of animals. Female figurines have been found within bins used for storage of cereals, such as wheat and barley, and the figurines are presumed to be of a deity protecting the grain. Peas were also grown, and almonds, pistachios, and fruit were harvested from trees in the surrounding hills. Sheep were domesticated and evidence suggests the beginning of cattle domestication as well. However, hunting continued to be a major source of food for the community. Pottery and obsidian tools appear to have been major industries; obsidian tools were probably both used and also traded for items such as Mediterranean sea shells and flint from Syria.

Excavations at the southern area of the site

Earliest known textile fragments

Images of deities

Mural of aurochs, a deer, and humans

Relief of two lionesses facing each other

Aurochs' heads

A photo of the earliest excavations in Çatalhöyük.

A striking feature of Çatalhöyük are its female figurines. Mellaart, the original excavator, argued that these well-formed, carefully made figurines, carved and molded from marble, blue and brown limestone, schist, calcite, basalt, alabaster, and clay, represented a female deity. Although a male deity existed as well, "statues of a female deity far outnumber those of the male deity, who moreover, does not appear to be represented at all after Level VI".[24] To date, eighteen levels have been identified. These artfully-hewn figurines were found primarily in areas Mellaart believed to be shrines. The stately goddess seated on a throne flanked by two female lions (illustration) was found in a grain bin, which Mellaart suggests might have been a means of ensuring the harvest or protecting the food supply.[25] In later cultures, similar depictions are seen of Cybele, a mountain goddess.

Whereas Mellaart excavated nearly two hundred buildings in four seasons, the current excavator, Ian Hodder, spent an entire season excavating one building alone.[26] Hodder and his team, in 2004 and 2005, began to believe that the patterns suggested by Mellaart were false. They found one similar figurine, but the vast majority did not imitate the Mother Goddess style that Mellaart suggested. Instead of a Mother Goddess culture, Hodder points out that the site gives little indication of a matriarchy or patriarchy.

There are full breasts on which the hands rest, and the stomach is extended in the central part. There is a hole in the top for the head which is missing. As one turns the figurine around one notices that the arms are very thin, and then on the back of the figurine one sees a depiction of either a skeleton or the bones of a very thin and depleted human. The ribs and vertebrae are clear, as are the scapulae and the main pelvic bones. The figurine can be interpreted in a number of ways - as a woman turning into an ancestor, as a woman associated with death, or as death and life conjoined. It is possible that the lines around the body represent wrapping rather than ribs. Whatever the specific interpretation, this is a unique piece that may force us to change our views of the nature of Çatalhöyük society and imagery. Perhaps the importance of female imagery was related to some special role of the female in relation to death as much as to the roles of mother and nurturer.[27]

In an article in the Turkish Daily News, Hodder is reported as denying that Çatalhöyük was a matriarchal society and quoted as saying "When we look at what they eat and drink and at their social statues, we see that men and women had the same social status. There was a balance of power. Another example is the skulls found. If one's social status was of high importance in Çatalhöyük, the body and head were separated after death. The number of female and male skulls found during the excavations is almost equal."[28] In another article in the Hurriyet Daily News Hodder is reported to say "We have learned that men and women were equally approached".[29]

In a report in September 2009 on the discovery of around 2000 figurines Hodder is quoted as saying:

Çatalhöyük was excavated in the 1960s in a methodical way, but not using the full range of natural science techniques that are available to us today. Sir James Mellaart who excavated the site in the 1960s came up with all sorts of ideas about the way the site was organised and how it was lived in and so on... We’ve now started working there since the mid 1990s and come up with very different ideas about the site. One of the most obvious examples of that is that Çatalhöyük is perhaps best known for the idea of the mother goddess. But our work more recently has tended to show that in fact there is very little evidence of a mother goddess and very little evidence of some sort of female-based matriarchy. That’s just one of the many myths that the modern scientific work is undermining.[30]

Professor Lynn Meskell explained that while the original excavations had found only 200 figures, the new excavations had uncovered 2,000 figurines of which most were animals, with less than 5% of the figurines women.[30]

The current archaeological investigations at Çatalhöyük are supported by the following institutions and organizations:[33][34]


serena williams vs justine henin head to head

As of June 30, 2013, Williams leads the overall head-to-head series, 8â€“6.[5] Henin retired for the second time in January 2011.[6]

Henin–S. Williams rivalry

Tennis players Justine Henin from Belgium, former world No. 1, and Serena Williams from the USA, also former World No. 1,[1] [2] who met 14 times during their careers. When Henin was an active player, their rivalry was one of the most heated and competitive between two female players on the WTA Tour;[3] their contests were not solely athletic in nature, but interpersonal as well.[4]