Which SSRI to prescribe?
Individual selective serotonin reuptake inhibitors (SSRIs) are proving superior in treatment of certain subgroups of depressed patients, according to a review conducted at the University of Vienna.*
The premise for comparing SSRIs among themselves arose from the fact that, unlike tricyclic antidepressants (TCAs), SSRIs have very different molecular structures. Thus certain patients might benefit more from one SSRI than another. It also implies that some inadequately-responding users might benefit by switching SSRIs.The reviewers' findings are outlined below. Each bulleted item reflects comparisons of only two or three drugs, not the overall group. The findings are based on a small number of trials, and more research is needed. Nonetheless, the results are provocative.
General considerations
SSRIs are more effective than TCAs and have better safety and compliance profiles. Specific findings included:
* fluvoxamine reduced Hamilton Depression Rating Scale (HAMD) scores insignificantly more than paroxetine;
* paroxetine and fluoxetine had comparable efficacy and safety;
* fluvoxamine reduced HAMD total scores one point more than sertraline, but sertraline caused significantly more sexual dysfunction and libido problems .
* sertraline and fluoxetine had similar efficacy and adverse effects, but there was more agitation, anxiety, and insomnia in the fluoxetine group.
Severe depression
Trials among severely depressed patients yielded the following results:
* fluoxetine and paroxetine had efficacy similar to other antidepressants;
* citalopram, fluoxetine, and paroxetine might be less effective than TCAs in hospitalized patients;
* fluvoxamine had significantly more efficacy than placebo or imipramine; efficacy of imipramine and placebo were approximately equal;
* fluvoxamine had a faster onset of action in individual HAMD categories such as depressed mood, suicide, and psychic anxiety.
Suicidal thoughts
As a rule, SSRIs do not cause suicidal tendencies. Trials revealed the following:
* fluvoxamine produced a faster decline in suicidal tendencies than did imipramine or placebo;
* paroxetine was no more effective than amitriptyline;
* fluoxetine could cause akathisia, which might promote suicidal ideation.
Anxiety
SSRIs are, in general, the antidepressant most suited for
depressed patients with anxiety. However, there are some differences within the class:* fluoxetine caused anxiety and agitation in 15-19% of patients; paroxetine affected about 8% of patients; sertraline affected approximately 6%;
* fluvoxamine affected only about 1% of patients and was effective for panic disorder;
* fluvoxamine and lorazepam were equally effective;
* fluoxetine and paroxetine had similar profiles in onset of antidepressant effect;
* paroxetine resolved symptoms of anxiety earlier than fluoxetine did, but both were equally effective after six-weeks; fluoxetine caused slightly more adverse effects.
Some studies produced conflicting conclusions; the reviewers suggest that these might be due to differences in dosage or in outpatient/inpatient status.
Geriatrics
Unlike TCAs, SSRIs are not associated with clinically significant anticholinergic side effects, cardiotoxicity, impaired psychomotor or cognitive performance, or suicidal behavior. As a class, SSRIs are a good alternative to TCAs for the elderly. Some specific findings:
* fluvoxamine and imipramine were significantly superior to placebo, but imipramine caused toxic confusion in four patients;
* nortriptyline was more effective than fluoxetine in multimorbid elderly depressed patients;
* fluoxetine caused more side effects than did sertraline;
* paroxetine produced greater initial benefit than did fluoxetine; paroxetine produced greater improvement in cognitive function; there were no differences in side effects;
* sertraline produced greater improvement in cognitive function than did fluoxetine.
Long-term treatment
Several points were raised by studies of long-term treatment:
* SSRIs were superior to placebo;
* fluvoxamine was superior to imipramine;
* paroxetine was tolerated better than imipramine;
* new-generation antidepressants were effective in preventing recurrence or relapse.
Summary
The paucity of data makes it difficult to directly compare the various SSRIs, but it appears that currently available SSRIs have more similarities than differences. All are effective in acute and long-term treatment of depression. Because they have different pharmacodynamic and pharmacokinetic properties, further research might spur differences in usage patterns. The preliminary findings are certainly thought-provoking.
* Kasper S, Heiden A: Do SSRIs differ in their antidepressant efficacy. Human Psychopharmacol 1995;10:S163-S172.
