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What Medicines are Used to Treat Atypical Depression?

written by: ChrisOM • edited by: Paul Arnold • updated: 10/2/2010

Atypical depression is often treated with different medicines to typical depression. This article explores some of the medicines that are most commonly used, how they work and the benefits they bring.

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    Atypical depression vs typical depression

    Atypical depression is a significant subtype of major depressive disorder (MDD). It differs from the less common “typical” depression in that the sufferer’s mood can improve in response to stimuli, and the sufferer displays two or more of the following: hypersomnia, leaden paralysis and chronic sensitivity to interpersonal rejection. While treatment prescribed for typical and atypical depression is often the same, recent research has shown that the two groups tend to respond slightly differently to the same medications. This article will explore some of the medicines used to treat atypical depression, their effectiveness, and how they work.

    The most popular theory on how antidepressants work is called the monoamine hypothesis. It proposes that antidepressants keep the neurotransmitters called monoamines (serotonin, noradrenalin, melatonin and dopamine, among others) present in the brain in a useable form for longer than usual. The hypothesis suggests that people with depression have lower levels of certain neurotransmitters in the brain than the general population, and raising these levels should eliminate the depression.

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    How they work: Selective Serotonin Reuptake inhibitors (SSRIs) are arguably the most commonly prescribed antidepressants in the western world. It is thought that SSRIs work by keeping the neurotransmitter serotonin present in the synapse for longer than would otherwise be possible, thus raising the level of serotonin in the brain.

    Effectiveness: A number of studies (including Henkel et al., 2010) have found SSRIs such as sertraline to be no more effective than placebo in cases of atypical depression. Citalopram, in particular, has been found to be less effective in patients with atypical depression. A small number of studies have found fluoxetine, another SSRI, to be as effective as MAOIs (see below) in treating atypical depression (Pande et al., 1996; Llonqvist et al., 1994).

    Benefits: SSRIs have fewer side effects than other types of antidepressants, and the side effects that they have tend to be better tolerated.

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    How they work: Serotonin and Noradrenaline Reuptake inhibitors (SNRIs) are thought to work by keeping the neurotransmitters serotonin and noradrenaline active in the synapse for longer than would otherwise be possible.

    Effectiveness: There is preliminary evidence that duloxetine may cause response in up to 50% of patients with atypical depression.

    Benefits: The benefits of SSRIs apply to SNRIs too. The reasonably common side effect of weight loss seen with SNRI use may be seen as a benefit in the case of atypical depression, which is associated with overeating. SNRIs are also less likely than SSRIs to cause sedation.

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    How they work: Tricyclic antidepressants (TCAs) work mainly to inhibit the reuptake of serotonin and noradrenaline. They may also have mild effects on dopamine levels in the brain. TCAs also act on the levels of other neurotransmitters and mineral levels in the brain.

    Effectiveness: TCAs, specifically imipramine, have been found to be much less effective than other antidepressants such as MAOIs in treating atypical depression (Quitkin et al., 1988; Quitkin et al., 1990). There little evidence of TCAs being appropriate as medicines used to treat atypical depression, and now are not recommended for this purpose (Henkel, 2010).

    Benefits: TCAs tackle a wide range of disorders, such as many anxiety disorders, eating disorders, some personality disorders and irritable bowel syndrome. Thus they may be useful if a patient suffers from one or more of these conditions, in addition to atypical depression.

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    How they work: Monoamine oxidase inhibitors (MAOIs) inhibit the breakdown of monoamines (e.g. serotonin, noradrenalin), keeping them active in the brain for longer.

    Effectiveness: MAOIs (in particular phenelzine) have been consistently found to be more successful than TCAs in treating atypical depression, with the difference between the two categories becoming more pronounced as treatment continues. A study by Liebowitz et al. (1988) showed that 71% of patients who self identified as having atypical depression responded to phenelzine, compared to 50% who responded to imipramine and 28% who responded to a placebo. This is in contrast to patients with typical depression, who are much more likely to respond to TCAs.

    Benefits: As well as being highly effective in the treatment of atypical depression, MAOIs have been found to reduce somnolence, which is often desirable for patients suffering with hypersomnia. However, MAOIs are often not used as first-line treatment due to the associated dietary restrictions and large number of side effects.

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    American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: American Psychiatric Association.

    Henkel, V., Mergl, R., Allgaier, A. K., Hautzinger, M., Kohnen, R., Coyne, J. C., Moeller, H. J. & Hegerl. (2010). Treatment of atypical depression: Post-hoc analysis of a randomised controlled study testing the efficacy of sertraline and cognitive behavioural therapy in mildly depressed outpatients. European Psychiatry, in press.

    Liebowitz, M. R., Quitkin, F. M., Stewart, J. W., McGrath, P. J., Harrison, W. M., Markowitz, J. S. et al. (1988). Antidepressant specificity in atypical depression. Archives of General Psychiatry, 45 (2), 129-137.

    Liebowitz, M. R., Quitkin, F. M., Stewart, J. W., McGrath, P. J., Harrison, W. M., Markowitz, J. S. et al. (1984). Phenelzine v Imipramine in atypical depression: A preliminary report. Archives of General Psychiatry, 41 (7), 669-677.

    Lonnqvist, J., Sihivo, S., Syvdahti, E. & Kiviruusu, O. (1994). Moclobemide and fluoxetine in atypical depression: a double blind trial. Journal of Affective Disorders, 32, 169-177.

    Quitkin, F. M., Harrison, W., Stewart, J. W., McGrath, P. J., Tricamo, E., Ocepek-Welikson, K. et al. (1991). Response to phenelzine and imipramine in placebo nonresponders with atypical depression: A new application of the crossover design. Archives of General Psychiatry, 48 (4), 319-323.

    Quitkin, F. M., McGrath, P. J., Stewart, J. W., Harrison, W., Tricamo, E., Wager, S. G. et al (1990). Atypical depression, panic attacks and response to imipramine and phenelzine. A replication. Archives of General Psychiatry, 47, 935-941.

    Pande, A. C., Birkett, M., Fechner-Bates, S., Haskett, R. F. & Greden, J. F. (1996). Fluoxetine versus phenelzine in atypical depression. Biological Psychiatry, 40, 1017-1020.

    Preskorn, S. H., Ross, R. & Stanga, C.Y. (2004). Selective Serotonin Reuptake Inhibitors. In: Sheldon H. Preskorn, Hohn P. Feighner, Christina Y. Stanga and Ruth Ross. Antidepressants: Past, Present and Future. Berlin: Springer. 241–62.

    Stewart, J. W., McGrath, P. J., Fava, M., Wisniewski, S. R., Zisook, S., Cook, I. et al. (2010). Do atypical features affect outcome in depressed outpatients treated with citalopram? International Journal of Neuropsychopharmacology, 13, 15-30.

    Stewart, J. W., Deliyannides, D. A. & McGrath, P. J. (2008). Is duloxetine effective treatment for depression with atypical features? International Journal of Clinical Psychopharmacology, 23 (6), 333-336.