Search

There is a high incidence of sexual dysfunction in the general population and sexual dysfunction is often an integral symptom of a depressive disorder. In addition, all antidepressants have effects on sexual functioning, as the result of side-effects of these medications and as a reflection of therapeutic success. The selective serotonin reuptake inhibitors (SSRIs) are clearly associated with delayed ejaculation, inability to ejaculate and absent or delayed orgasm. Furthermore, the incidence of sexual dysfunction obtained by patient self- report does not appear to reflect the true incidence of sexual dysfunction associated with antidepressant therapy and systematic inquiry is needed as sexual dysfunction may be an unrecognized cause of non- compliance. The SSRIs may have advantageous effects on sexual functioning and these may also be under- reported due to the same factors resulting in an under-reporting of sexual side-effects in general. In addition, studies have suggested a role for the SSRIs in the management of premature ejaculation. The effects of SSRIs on sexual functioning are clearly dose-related and may vary amongst the group due to their relative effects on the serotonin and dopamine systems and the extent to which plasma levels of these drugs accumulate in the body over time. A variety of strategies have been found useful in the management of SSRI-induced sexual dysfunction including waiting for tolerance to develop, dosage reduction, drug holidays, switching to a different antidepressant and various augmentation strategies with 5-HT 2, α2 adrenergic receptor antagonists and dopamine receptor agonists.

The highly specific mechanism of action of the selective serotonin re-uptake inhibitors (SSRIs) confers advantages on this group, relative to other classes of antidepressant, and thus represents a significant advance in the pharmacotherapy of depression. Whilst their clinical efficacy is equivalent to that of the tricyclic antidepressants (TCAs), the SSRIs have a greatly reduced risk of toxicity in overdose and have been shown to be significantly better tolerated. Specifically, the SSRIs have a low incidence of anticholinergic effects and are essentially devoid of cardiotoxicity. This tolerability advantage may be of significance in improving compliance and hence cost-effectiveness of treatment, particularly in the long term. 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, the SSRIs have been shown to be effective in obsessive-compulsive disorder, panic disorder and social phobia. Although superior efficacy has not been demonstrated for any one of the SSRIs, the structural diversity of this group is reflected in emerging qualitative and quantitative differences in side effects and drug interaction potential. Many of these differential features reflect important variations in pharmacological and pharmacokinetic profiles, including dosage flexibility, washout times, dose-plasma level proportionality and age-related changes in plasma levels. Fluoxetine, for example, has a considerably longer half-life than other SSRIs and side effects and drug interactions may thus occur for an extended period following discontinuation of treatment. Significant differences in the potential for drug interactions in this group are related to their relative potency for inhibition of important liver drug-metabolising enzymes including CYPIID6, CYPIA2 and CYPIIA4. Large comparative clinical trials of the different SSRIs have yet to be undertaken; however, the differences that have already become apparent provide important information enabling the physician to choose an SSRI appropriate to the individual patient.

The long-term outlook for patients with unipolar depression is often poor. As few as one-fifth will remain well and a similar number will suffer chronic depression. It is now standard practice to extend acute treatment into a 4–6 month period of continuation therapy, and the value of prophylactic treatment over longer periods is becoming more widely recognised. Care must, however, be exercised in choosing suitable long-term treatment. Relatively little work on the prophylactic efficacy of the tricyclic antidepressants has been carried out, although imipramine has been shown to be effective. The selective serotonin re-uptake inhibitors (SSRIs) have been studied extensively and may be the most suitable long-term treatment for depression. Sertraline is effective in preventing both relapse and recurrence of depression and was the first agent specifically indicated for the long-term treatment of depression in the UK. In addition to clinical efficacy, many other factors favour SSRIs in the long-term management of depression. The tolerability of a drug is of major importance in long-term therapy since it affects compliance. Other important considerations include toxicity, safety in overdose, drug interaction potential, psychomotor effects and accident liability.