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Comparative Efficacy of Antidepressants

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Summary

Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of drugs with significantly greater antidepressant efficacy than placebo. Generally, in double-blind comparative trials, all SSRIs demonstrated antidepressant efficacy similar to that of the ‘standard’ tricyclic antidepressants amitriptyline and imipramine; a meta-analysis of controlled trials found the efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless, because of small patient numbers included in most studies that compare SSRIs with other antidepressants, no definitive statements about relative efficacy can be made. In these studies it is simply possible to state that no statistically significant differences were identified between SSRIs and the comparative antidepressants. Importantly, differences in clinical characteristics exist between the SSRIs — differences in elimination half-life (t½β) between fluoxetine and/or its metabolite (total t½β = 330 hours) and other SSRIs (t½β range = 15 to 30 hours), for example. This has implications in terms of potential drug interactions and must be considered when patients have to be switched to treatment with monoamine oxidase inhibitors.

Studies with fluvoxamine have been conducted in both in- and outpatients, whereas trials with other SSRIs have been confined largely to outpatient populations. Fluvoxamine has been associated with a high incidence of nausea (37%), although this may have resulted from high initial dosages (rather than upward dose titration protocols) used in early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to produce a satisfactory antidepressant response, and this SSRI may be particularly useful in patients with chronic retarded depression. More clinical data are required before the efficacy of sertraline and citalopram relative to standard antidepressants can be clearly defined. Preliminary data indicate that SSRIs are effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger, impulsiveness) and substance abuse (e.g. alcoholism); early results with fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in the treatment of bulimia, personality disorders and alcohol abuse, have been encouraging.

SSRIs have a more favourable tolerability profile than tricyclic antidepressants and, unlike the tricyclics, are not associated with anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs are associated with a relatively high incidence of nausea, particularly if high doses are used at the start of treatment. However, the incidence of nausea appears to decrease as treatment is continued. Although SSRIs appear to be well tolerated, they are a new drug class and, thus, patients should be monitored carefully for the occurrence of unexpected adverse reactions (e.g. the ‘flu-like’ illness noted in a small number of zimeldine recipients).

Overall, SSRIs have been shown to be effective and safe agents for the treatment of patients with major depressive disorders. These drugs possess tolerability advantages over tricyclic antidepressants, and preliminary evidence suggests that they may have future value in the treatment of panic disorder, OCD, eating and personality disorders, and substance abuse.

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  1. Psychiatric Department, University of Bonn, Sigmund Freudstrasse 25, D-5300, Bonn, Federal Republic of Germany

    S. Kasper, J. Fuger & H.-J. Möller

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Kasper, S., Fuger, J. & Möller, HJ. Comparative Efficacy of Antidepressants. Drugs 43 (Suppl 2), 11–23 (1992). https://doi.org/10.2165/00003495-199200432-00004

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