Antidepressant Side Effects in Depression Patients Treated in A Naturalistic Setting: A Study of Bupropion, Moclobemide, Paroxetine, Sertraline, and Venlafaxine

JD Vanderkooy, BSc1, Sidney H Kennedy, MD, FRCPC2,4, R Michael Bagby, PhD, CPsych3,4

Objective: There is no commonly accepted standard for comparing antidepressant-induced side effects. This study evaluates a clinician-administered scale, the Toronto Side Effect Scale (TSES), in a natural practice clinic.

Method: We used the TSES to assess side effects in 193 depression patients who completed 8 weeks of treatment with either bupropion, moclobemide, paroxetine, sertraline, or venlafaxine.

Results: Rates of remission (Hamilton Rating Scale for Depression [HRSD] < 7) did not differ across drugs after 8 weeks of treatment. Paired drug comparisons yielded significant differences in 16 of the 32 side effects. We present differences between pairs of the 5 antidepressants in Central Nervous System (CNS), gastrointestinal (GI), and sexual side effects. A measure of side-effect intensity distinguished paroxetine from the other antidepressants on a measure of sexual dysfunction.

Conclusions: These results confirm the clinical utility of the TSES as a simple, clinician-administered antidepressant side-effect scale.

(Can J Psychiatry 2002;47::174–180)

Clinical Implications

The Toronto Side Effect Scale (TSES) may be a useful side-effect measure for clinicians.
The clinical impression is confirmed that side effects distinguish antidepressants more than rates of remission.
Intensity of side effects as measured by the TSES did not provide added value to clinicians.

Limitations

This study was not a randomized placebo-controlled design, although it was a good reflection of natural practice.
The sample size for moclobemide and bupropion was relatively small, compared with that for paroxetine, sertraline, and venlafaxine.
Patients were not evaluated for longer than 8 weeks.

Key Words: sexual side effects, bupropion, moclobemide, paroxetine, sertraline, venlafaxine, major depressive disorder, naturalistic

Résumé : Effets secondaires des antidépresseurs chez des patients dépressifs traités dans un cadre naturel : une étude du bupropion, du moclobémide, de la paroxétine, de la sertraline et de la venlafaxine

Because therapeutic efficacy across antidepressants (ADs) is generally comparable, most clinicians perceive differences in the incidence of side effects to be an important factor in their selection of ADs (1). However, very few studies have directly compared side effects across the selective serotonin reuptake inhibitors (SSRIs) and other novel ADs. Instead, clinicians rely on information from standard references, such as the Physicians’ Desk Reference (PDR) (2) or Compendium of Pharmaceuticals and Specialties (CPS) (3), and occasionally on metaanalyses of side effects derived from clinical trials (4).

This investigation compares the side effects of 5 frequently prescribed AD medications (venlafaxine, a serotonin and norepinephrine reuptake inhibitor [SNRI]; paroxetine and sertraline, SSRIs; moclobemide, a reversible inhibitor of monoamine oxidase A [RIMA]; and bupropion, a norepinephrine and dopamine modulator [NDM]) in a sample of depression patients who were assessed and treated under natural practice conditions in an outpatient clinic. We proposed to demonstrate differences in class-specific prevalences of side effects consistent with those found in metaanalyses and randomized controlled trials (RCTs). We also proposed that intensity, as a product of frequency and severity of side effects, would further differentiate ADs, both across and within classes.

Method

Our subjects were outpatients with unipolar, nonpsychotic major depressive disorder (MDD) who provided informed consent and were treated at the Depression Clinic, Centre for Addiction and Mental Health (CAMH), a tertiary care facility affiliated with the University of Toronto. Entry criteria were a current diagnosis of major depressive episode (MDE) according to DSM-IV criteria, a score of 16 or greater on the 17-item Hamilton Rating Scale for Depression (HRSD-17) (5), absence of concurrent active medical illness, absence of AD or other psychotropic medications for a minimum of 2 weeks (5 weeks for fluoxetine), and absence of exposure to electroconvulsive therapy (ECT) for at least 3 months prior to treatment initiation. The study was approved by the CAMH Research Ethics Board.

Measure and Design

The Toronto Side Effect Scale (TSES) is a 32-item instrument that uses direct physician inquiry to elicit adverse events. Modified from a previous instrument developed by Healy (6), the TSES is designed to establish incidence, frequency, and severity of central nervous system (CNS), gastrointestinal (GI), and sexual side effects (see Appendix). For each side effect, frequency and severity were measured on a 5-point Likert scale. An “intensity” score was derived by multiplying frequency by severity.