Antidepressant Antidepressant American Airlines Category="Antidepressants"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), myofascial 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.

History

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.

Efficacy of antidepressants in question

Several studies have stimulated doubt about the effectiveness of antidepressants. The studies cite that the difference between antidepressants and placebo is neglible. Antidepressants work only slightly better than dummy pills, and the Food and Drug Administration has not informed physicians of how little benefit most of these depression drugs offer, suggests a study:

Kirsch I, Moore TJ, Scoboria A, Nicholls SS (2002a), The emperor's new drugs: an analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment 5:Article 23. Available at: journals.apa.org/prevention/volume5/toc-jul15-02.html

Through a Freedom of Information Act request, two psychologists obtained 47 studies used by the FDA for approval of the six antidepressants prescribed most widely between 1987-99. Overall, antidepressant pills worked 18 percent better than placebos, a statistically significant difference, "but not meaningful for people in clinical settings," says University of Connecticut psychologist Irving Kirsch. He and co-author Thomas Moore released their findings in "Prevention and Treatment," an e-journal of the American Psychological Association.

More than half of the 47 studies found that patients on antidepressants improved no more than those on placebos, Kirsch says. "They should have told the American public about this. The drugs have been touted as much more effective than they are." He says studies finding no benefit have been mentioned only on labeling for Celexa, the most recently approved drug. The others included in his evaluation: Prozac, Paxil, Zoloft, Effexor and Serzone.

Similar studies:

Hollon SD, DeRubeis RJ, Shelton RC, Weiss B (2002), The emperor's new drugs: effect size and moderation effects. Prevention & Treatment 5:Article 28. Available at: journals.apa.org/ prevention/volume5/toc-jul15-02.html.

Jacobson NS, Roberts LJ, Berns SB, McGlinchey JB (1999), Methods for defining and determining the clinical significance of treatment effects: description, application, and alternatives. J Consult Clin Psychol 67(3):300-307.

Kirsch I, Sapirstein G (1998), Listening to Prozac but hearing placebo: a meta analysis of antidepressant medication. Prevention & Treatment 1: Article 0002a. Available at: journals.apa.org/prevention/volume-1/toc-jun26-98.html. Accessed Aug. 2, 2002.

Kirsch I, Scoboria A, Moore TJ (2002b), Antidepressants and placebos: secrets, revelations, and unanswered questions. Prevention & Treat-ment 5:Article 33. Available at: www.journals. apa.org/prevention/volume5/toc-jul15-02.html. Accessed Aug. 2.

Klein DF (1998), Listening to meta-analysis but hearing bias. Prevention & Treatment 1:Article 0006c. Available at: www.journals.apa.org/prevention/volume 1/toc-jun26-98.html. Accessed Aug. 2, 2002.

Thase ME (2002), Antidepressant effects: the suit may be small, but the fabric is real. Prevention & Treatment 5:Article 32. Available at: journals.apa.org/prevention/volume5/toc-jul15-02.html. Accessed Aug. 2.

Walach H, Maidhof C (1999), Is the placebo effect dependent on time? A meta-analysis. In: How Expectancies Shape Experience, Kirsch I, ed. Washington, D.C.: American Psychological Association, pp321-332.

Moncrieff, J., Wessely, S., and Hardy, R. (1998). Meta-analysis of trials comparing antidepressants with active placebos. British Journal of Psychiatry 172: 227-231.

Parker, G., Anderson, I.M., and Haddad, P. (2003). Clinical trials of antidepressant medications are producing meaningless results. British Journal of Psychiatry 183(2): 102-104.

Enserlink, M. (1999). Psychopharmacology: can the placebo be the cure? Science 284: 238-240

Side effects

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. One exception to this is Bupropion, which in many cases results in a moderately increased libido. Some clinicians have found that adding bupropion to a regimen of SSRI medications can sometimes alleviate some degree of sexual dysfunction. However, the mechanism of action for bupropion 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

Classes

See also: List of antidepressants

Prominent members

Well-known antidepressants are:

Antidepressant treatment strategies

On efficacy measures, a successful antidepressant trial involves just 50 percent or more of the test subjects on the drug responding to the medication. “Response” signifies a mere 50 percent or greater reduction in depression symptoms as opposed to “remission,” which indicates a virtual elimination of depression symptoms. A number of different treatment strategies, however, may produce better results:

Switching antidepressants

The American Psychiatric Association 2000 Practice Guideline for the Treatment of Patients with Major Depressive Disorder 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 series of open-label studies by Michael Thase MD of the University of Pittsburgh found that more than half the patients who failed on their initial antidepressant achieved a response on their second antidepressant from the same class. (Thase ME et al. "Fluoxetine treatment of patients with major depressive disorder who failed initial treatment with sertraline." J Clin Psychiatry. 1997 Jan;58(1):16-21.) A 2002 double-blind study by the same author found a positive benefit among treatment-resistant patients switching either from an SSRI to a tricyclic or from a tricyclic to an SSRI. (Thase ME et al. "Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression." Arch Gen Psychiatry. 2002 Mar;59(3):233-9.)

Augmenting and combining antidepressants

For a partial response, the American Psychiatric Association advises augmenting an antidepressant with a different pharmaceutical agent. These agents may include Lithium, thyroid supplementation, atypical antipsychotics, and dopamine agonists, among others. Symbyax a combination olanzapine-fluoxetine (Zyprexa-Prozac) pill is approved in the US for treating bipolar depression, and is being investigated for other depression indications. In general, however, there are no major augmentation studies to guide psychiatrists.

Combination strategy involves using two or more antidepressants from different classes to target different more than one neurotransmitter in order to hopefully achieve a more beneficial result. Again, this is a little-studied area of antidepressant treatment. (See article.)

Combining antidepressant treatment with psychotherapy

A 2000 study found that those on nefazadone (Serzone) plus a form of short-term psychotherapy called Cognitive Behavioral Analysis System of Psychotherapy (CBASP) fared significantly better (85 percent response, 42 percent remission) than those on Serzone alone (55 percent response, 22 percent remission) or CBASP alone (52 percent response, 24 percent remission). (Keller MB et al. "A comparison of nefazadone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression." N Engl J Med. 2000 May 18;342(20):1462-70.) (See article.)

Preventing relapse

A 2003 meta-analysis of 31 placebo-controlled antidepressant trials found that continuing with antidepressants reduced the risk of relapse by 70 percent. (Geddes JR et al. "Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review." Lancet. 2003 Feb 22;361(9358):653-61.)

The American Psychiatric Association advises four to five months of continuation treatment on an antidepressant following the resolution of symptoms. For patients with a history of depressive episodes, the British Association for Psychopharmacology's 2000 Evidence Based Guidelines for Treating Depressive Disorders with Antidepressants advises remaining on an antidepressant for at least six months and as long as five years or indefinitely. (See article)

Alternative medicine

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.

References

External links