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An antidepressant is a medication used primarily in the treatment of clinical depression. Modern antidepressants are not stimulants and are not generally addictive. They also are not thought to produce tolerance, although sudden withdrawal may produce adverse effects. Antidepressants create little if any immediate change in mood and require between several days and several weeks to take effect.
Some antidepressants, notably the tricyclics, are commonly used off-label in the treatment of neuropathic pain, whether or not the patient is depressed. Smaller doses are generally used for this purpose, and they often take effect more quickly.
Many antidepressants also are used for the treatment of anxiety disorders, and tricyclic antidepressants are used in the treatment of chronic pain disorders such as Chronic Functional Abdominal Pain (CFAP), Myofacial Pain Syndrome, and post-herpetic neuralgia.
Like many psychiatric drugs, antidepressants were discovered by accident. The first antidepressants, imipramine, a tricyclic, and iproniazid, a monoamine oxidase inhibitor, were discovered in the 1950s. These drugs were found to have the side effect of improving the patients' mood. However, the newer SSRI antidepressants were early examples of rational drug design.
How they are believed to work
The therapeutic effects are believed to be related to an effect on neurotransmitters, particularly by inhibiting the monoamine transporter proteins of serotonin and norepinephrine. Selective serotonin reuptake inhibitors (SSRIs) specifically prevent the reuptake of serotonin (thereby increasing the level of serotonin in synapses of the brain), whereas earlier monoamine oxidase inhibitors (MAOIs) blocked the destruction of neurotransmitters by enzymes which normally break them down. Although these drugs are clearly effective in treating depression, the current theory still leaves unanswered questions. For example, concentrations in the blood build to therapeutic levels in only a few days and begin affecting neurotransmitter activity immediately. Changes in mood, however, often take four weeks or more to appear. One explanation holds that the "down-regulation" of neurotransmitter receptors-an apparent consequence of excess signaling and a process that takes several weeks-is actually the mechanism responsible for the alleviation of depressive symptoms. Another theory, based on recent research published by the National Institutes of Health in the United States, suggests that antidepressants may derive their effects by promoting neurogenesis in the hippocampus.
Antidepressants can often cause side effects, and an inability to tolerate these is the most common cause of discontinuing the medication. Sexual dysfunction is a very common side effect. Although recent drugs have fewer side effects, patients sometimes report severe side effects associated with their discontinuation, particularly with Paroxetine. Additionally, certain patients do not respond to antidepressant drugs.
Antidepressants may actually make the mania component of bipolar disorder worse, and should be used with great care in the treatment of that disorder, usually in conjunction with mood stabilisers. Their use should be monitored by a psychiatrist, but in countries such as Britain, New Zealand and the United States, primary care physicians are able to prescribe antidepressents without consulting a psychiatrist. In particular, it has been noted that the most dangerous period for suicide in a patient with depression is immediately after treatment has commenced, as antidepressants may reduce the symptoms of depression such as psychomotor retardation or lack of motivation before mood starts to improve.
Classes of antidepressant
• Roberto Delle Chiaie, Paolo Pancheri and Pierluigi Scapicchio. (2002). Efficacy and tolerability of oral and intramuscular S-adenosyl- L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr, 76 (5): 1172S-1176S
• Mischoulon D, Fava M. (2002). Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr, 76 (5): 1158S-61S.
• Hypericum Depression Trial Study Group (2002). Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder: A Randomized Controlled Clinical Trial. JAMA, 287 (14):1807-1814.
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