Do Depressed Patients With Diabetes Experience More Side Effects When Treated With Citalopram Than Their Counterparts Without Diabetes? A STAR*D Study

Major depressive disorder (MDD) is a serious mental health problem that affects approximately 16 million individuals in the United States.1 Current estimates show that the majority of these individuals receive little or no treatment.2 Major depressive disorder is associated with high morbidity and mortality,3 profound mental and physical impairment, and losses in work productivity, which can result in high indirect and direct societal costs.2 Major depressive disorder often occurs concurrently with serious medical comorbidities, such as cancer and diabetes mellitus (DM). Previous studies reported that individuals with DM are twice as likely to have MDD as are individuals without DM.4–6 The presence of major depressive disorder in patients with diabetes is a significant public health burden and is associated with hyperglycemia, increased diabetic complications and mortality,7 increased costs, and poorer adherence to a healthy diet and regular exercise.8 In addition, patients with diabetes and comorbid depression appear to experience more physical symptoms associated with diabetes than their nondepressed counterparts.9 Because MDD can be a risk factor for nonadherence with medical treatment,10 the appropriate treatment of MDD when it occurs concurrently with DM takes on increased importance since improvement in mood may improve glycemic control. Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants prescribed for the treatment of MDD. These drugs have revolutionized MDD treatment with advantages that include a better safety profile, benign side effects, a reduction in the likelihood of fatal cardiac events, ease of dose titration,11 and lower discontinuation rates.12 Tricyclic antidepressants and SSRIs have similar therapeutic effects; however, SSRIs have been reported to have a longer time to response (4–6 weeks) before changes in depression severity are observed.13 Clinical Points ♦ Participants with diabetes mellitus reported experiencing side effects from citalopram treatment at lower frequencies compared to those without diabetes mellitus. ♦ Participants with and without diabetes mellitus differed, but not significantly, in the types of side effects reported. The safety and efficacy of the SSRI citalopram have been reported in a large number of controlled clinical trials over the past 10 years.11 These studies have shown that citalopram is a reliable, effective antidepressant that can be used safely in many patient populations (eg, the elderly).14 Citalopram has also been shown to be effective in preventing the relapse and recurrence of MDD.15 The most common side effects associated with citalopram treatment are sleep disturbances, gastrointestinal disturbances (eg, nausea and vomiting), excessive sweating, headache, sexual dysfunction, and tremors. Citalopram was also included in the US Food and Drug Administration's black box warning for suicidality in pediatric use of antidepressants.16 Side effects often occur during treatment with antidepressants. Side effects can have a detrimental impact on patient adherence to treatment and can cause increased attrition in controlled studies.17,18 Further, clinicians need to understand and anticipate the impact of adverse events reported by depressed patients. When treating depression, clinicians must engage in a delicate balancing act, as they must not only anticipate and manage side effects but also determine the optimal dose of antidepressants required to effect sustained MDD remission. Given that individuals with MDD are twice as likely to have comorbid DM,4–6 it would be useful to know whether side effects from citalopram treatment differ in depressed patients with and without DM. Such information would help clinicians to adapt existing treatment modalities to individual patient needs and to better educate patients about what to expect during treatment, thus increasing the probability of patient adherence to the MDD treatment regimen. To date, only 5 controlled studies on the effect of antidepressant medication19–21 and/or psychotherapeutic treatments22,23 on depression in patients with DM have been reported in the scientific literature. These studies focused on the treatment of MDD in patients with DM and on improving glycemic control. Since then, 1 open-label study has demonstrated not only improved depression outcomes with antidepressant treatment, but also improved glycemic control during both acute and maintenance treatment phases.24 The frequency and type of side effects from antidepressant treatment were not discussed in these reports. In this current study, we report on the results of a secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, in which we sought to determine whether side effects from citalopram treatment differ in depressed patients with and without DM. The STAR*D study is the largest antidepressant medication trial conducted in the United States to date. The study used a measurement-based care approach and an automated feedback system to ensure adequate and safe antidepressant treatment delivery suitable for both clinical research and routine practice.25 The implementation of measurement-based care ensured that antidepressant medication treatment was optimal regarding dose and duration, yet flexible enough to ensure safety given the wide range of comorbid general medical and psychiatric disorders allowed in the trial. The STAR*D study offered a unique opportunity to examine the differences in side effects reported by patients with nonpsychotic MDD with and without DM who were treated with citalopram. To our knowledge, this is the first study to examine the frequency, intensity, and burden of side effects along with a characterization of the types of side effects experienced by depressed outpatients with and without DM who were being treated for nonpsychotic MDD in both primary and psychiatric care settings.