An antidepressant is a medication designed to treat or alleviate the symptoms of clinical depression. Antidepressants 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.
Antidepressants do not seem to have all of the same addictive qualities as other substances such as nicotine, caffeine, cocaine, or other stimulants. (There is, however, controversy on the definition of addiction.) Some argue that antidepressants do not meet the general requirements for the commonly-established view. While some antidepressants may cause dependence and withdrawal they do not seem to cause uncontrollable urges to increase the dose due to euphoria or pleasure. For example, if an SSRI medication is suddenly discontinued, it may produce both somatic and psychological withdrawal symptoms, a phenomenon known as "SSRI discontinuation syndrome" (Tamam & Ozpoyraz, 2002). When the decision is made to stop taking antidepressants it is common practice to “wean” off of them by slowly decreasing the dose over a period of several weeks.
It is generally not a good idea to take antidepressants without a prescription. The selection of an antidepressant and dosage suitable for a certain case and a certain person is a lengthy and complicated process, requiring the knowledge of a professional. Certain antidepressants can initially make depression worse, can induce anxiety, or can make a patient aggressive, dysphoric or acutely suicidal. In certain cases, an antidepressant can induce a switch from depression to mania or hypomania, can accelerate and shorten a manic cycle (i.e. promote a rapid-cycling pattern), or can induce the development of psychosis (or just the re-activation of latent psychosis) in a patient with depression who wasn't psychotic before the antidepressant.
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 of antidepressants 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. Tricyclic antidepressants (TCAs) prevent the reuptake of various neurotransmitters, including serotonin, norepinephrine, and dopamine. 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 side effects Sexual dysfunction is a very common side effect, especially with SSRIs. Occasionally the sexual side effects of SSRIs can persistent long after the medications have been discontinued, sometimes indefinitely (see links below). One exception to this is Wellbutrin (bupropion), which in many cases results in a moderately increased libido. Some clinicians have found that adding Wellbutrin to a regimen of SSRI medications can sometimes alleviate some degree of sexual dysfunction. However, the mechanism of action for Wellbutrin appears to be unique and quite different from other mood elevators, among these being a stimulant-like effect and concurrent insomnia, especially in the first few weeks of use. Moreover, some patients, as seen with most psycho-active drugs, cannot tolerate it at all.
Other side effects
- Although recent drugs may have fewer side effects, patients sometimes report severe side effects associated with their discontinuation, particularly with Paroxetine. Additionally, a certain percentage of patients do not respond to antidepressant drugs. Another advantage of some newer antidepressants is they can show effects within as few as five days, whereas most take four to six weeks to show a change in mood. However, some studies show that these medications might be even more likely to result in moderate to severe sexual dysfunction. However, there are medications in trials that appear to show an improved profile in regards to sexual dysfunction and other key side effects.
- MAO inhibitors can produce a lethal hypertensive reaction if taken with foods that contain the amino acid tyramine, such as cheese and wine. Likewise, lethal reactions to both prescription and over the counter medications have occurred. Any patient currently undergoing therapy with an MAO inhibiting medication should be monitored closely by the prescribing physician and always consulted before taking an over the counter or prescribed medication. Such patients should also inform emergency room personnel and information should be kept with one's identification indicating the fact that the holder is on MAO inhibiting medications. Some doctors even suggest the use of a medical alert ID bracelet.
- Antidepressants often make the manic 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 antidepressants 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. Although this appears to be a paradox, studies indicate the suicidal ideation is a relatively common component of the initial phases of antidepressant therapy, and it may be even more prevalent in younger patients such as pre-adolescents and teenagers. It is strongly recommended that other family members and loved ones monitor the young patient's behavior, especially in the first eight weeks of therapy, for any signs of suicidal ideation or behaviors.
Members of the class
- monoamine oxidase inhibitors (MAOIs)
- tricyclic antidepressants
- selective serotonin reuptake inhibitors (SSRIs)
- serotonin-norepinephrine reuptake inhibitors (SNRIs)
- selective noradrenaline reuptake inhibitors (NARIs)
- novel antidepressants
- tetracyclic antidepressants
Well-known antidepressants are:
- fluoxetine (Prozac, Sarafem, Fluctin, Fontex, Prodep, Fludep)
- sertraline (Zoloft, Lustral, Apo-Sertral, Asentra, Gladem, Serlift, Stimuloton)
- venlafaxine (Effexor)
- citalopram (Celexa, Cipramil, Talohexane)
- paroxetine (Paxil, Seroxat, Aropax)
- escitalopram (Lexapro, Cipralex)
- fluvoxamine (Luvox, Faverin)
- duloxetine (Cymbalta)
- bupropion (Wellbutrin)
Despite controversy, alternative treatments for depression such as the herbal remedy St John's wort and the amino acid derivative SAM-e have also gained popularity in recent years, although their effectiveness varies. Clinical trials have shown SAM-e to be as effective as standard antidepressant medication, with many fewer side effects (Delle Chiaie et al., 2002; Mischoulon and Fava, 2002). Most studies conclude that St. John's wort is usually as effective against depressions as other modern medication, again with fewer side effects, and it is widely prescribed for depression in Europe. However, a recent study showed St. John's wort to be no more effective than a placebo in cases of severe depression (Hypericum Depression Trial Study Group, 2002). Tryptophan dietary supplements, although banned in many countries due to impurities that caused a blood disease, have also been used as natural antidepressants. Dietary supplements of 5-HTP, a chemical the body forms from tryptophan and uses to make serotonin, have shown some promising research results but need further study.
- 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.