Chin Med J (Taipei) 1998;61:S161.

Selective Serotonin Re-uptake Inhibitors: Pharmacologic Profiles and Potential Therapeutic Indications and Distinctions

Hann-Kuang Jiang

Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, R.O.C.

Abstract

The highly specific mechanism of action of the selective serotonin reuptake inhibitors (SSRIs) confers advantages on this group, relative to other classes of antidepressants, and thus represents a significant advance in the pharmacotherapy of depression. All SSRIs appear to be more efficacious than placebo for the acute treatment of major depressive disorder (MDD). Short-term (six-week) efficiency was comparable with that of tricyclic antidepressants (TCAs) for the amelioration of MDD regarded as moderately in severity. Further comparative trials are clearly indicated to demonstrate the therapeutic benefits of SSRIs in specific populations (e.g., geriatric, severely ill), and to demonstrate sustained benefit with long-term prophylaxis. Despite a lack of sedative effect, there is evidence that SSRIs are more effective than TCAs in the treatment of depression with anxiety. In addition, it is indicated that antidepressants with a serotonergic profile appear clearly superior to uptake inhibitors acting preferentially on the noradrenaline synapse in most clinical conditions, and other potential indications for SSRIs include many wide-spectrum psychiatric disorders: obsessive-compulsive disorder, panic disorder, social phobia, bulimia nervosa, chronic pain syndrome, alcoholism, premenstrual syndrome (PMS/LLPDD) and impulsivity/irritability. Although superior efficacy has not been demonstrated for any one of the SSRIs (fluoxetine, fluvoxamine, citalopram, paroxetine and sertraline), their structural diversity is reflected in emerging qualitative and quantitative differences in side effects drug interaction potential. Pharmacokinetic profiles of the five SSRIs also reveal similar parametric values, and most quantitative differences are of limited clinical significance. Adverse effects are common but ordinarily mild and transient, primarily restricted to the gastrointestinal tract, central nervous system and sexual functions. Important differences in the prevalence or severity of these adverse effects await the accumulation of further clinical experience and the completion of additional comparative trials. Similarly, the propensity of SSRIs to inhibit LIM metabolism of other medications is currently under investigation, and are dependent to their relative potency for inhibition of important liver drug metabolizing enzymes including CYP IID6, IA2 and IIIA4 as recently findings. The most important SSRI-related potential interactions are with TCAs, MAOIs, tryptophan and lithium. In the future, these adverse interactions may be predicted by computer modelling and in vitro molecular modelling techniques, and the prescriber can then be provided with accurate information to improve the safety of patient care. Giving that the costs of these respective medications are comparable, all of the differences of SSRIs may ,ultimately serve to establish the preferential selection of individual agents in specific clinical situations and also, the appropriateness for the individual patient.

Keywords: SSRIs, pharmacologic profiles, side effects, interactions, cytochrome P-450 enzymes

[Chin Med J (Taipei) 1998;61:S161.]