Long-Term Exercise May Extend Remission in Depression
Regular exercise can extend remission from major depression, regardless of whether remission was initially achieved through exercise or medication, a new study suggests. Researchers conducted a one-year follow up on participants of the SMILE II study (Blumenthal JA et al, Psychosom Med 2007;69:587–596), to see if aerobic exercise had any effect on remission from major depressive disorder (MDD).
In the original SMILE II study, 202 patients with MDD were randomized to either 1) home-based exercise, 2) supervised exercise, 3) sertraline (Zoloft) up to 200 mg, or 4) pill placebo. At the end of the 16-week trial, patients in both exercise groups and the medication group showed similar improvements in HAM-D scores and MDD outcome classification (ie, depressed, partial remission, or full remission), and both were superior to placebo.
During the one-year follow up (16 months after the start of the trial), patients were allowed to choose their own treatment, such as exercise, Zoloft or some other antidepressant medication, or talk therapy, or they could choose to discontinue treatment. Of the original study sample, 85% (172 participants) provided follow-up data.
Forty-six percent of participants had been identified as fully remitted at the conclusion of the original 16-week trial (41% of the home exercise group; 54% of the supervised exercise group; 51% of the sertraline group; and 38% of the pill placebo group). One year after the trial ended, 66% were in full remission, and surprisingly, there were no significant differences in one-year remission rates among any of the groups, including placebo.
While there was no requirement that patients exercise during the one-year follow-up, about half said they did, and these patients had significantly lower HAM-D scores (less depression) than those who did not choose to exercise. This benefit of exercise was the same regardless of the initial treatment assignment. There was an inverse relationship between HAM-D scores and time spent engaging in moderate intensity exercise. People who reported exercising three hours per week had an average 3.1 point lower HAM-D score than those who reported not exercising at all. Improvement leveled off when exercise was increased to more than three hours per week (Hoffman BM et al, Psychosom Med 2010; online ahead of print).
TCPR’s Take: Past research shows a negative association between depression and exercise (Goodwin, Prev Med 2003;36:698–703), but has not clarified the causality question (ie, does exercise improve depression or do people who are depressed lack the motivation to exercise?). (For more on this topic, see TCPR, July/August 2010.) This study does not clarify the issue, because during the one-year follow up patients were not randomly assigned to exercise vs no exercise. Regardless, these findings are suggestive, and should encourage us to recommend exercise for our depressed patients.
Antidepressants Found Ineffective for Subthreshold Depression
Many patients come into our offices feeling demoralized or unhappy, but without meeting the full diagnostic criteria for major depression or dysthymia. We often prescribe antidepressants for these subthreshold patients, on the theory that there is probably a continuum of depression severity.
It makes intuitive sense that if a medication works for a severely depressed patient, it would be at least somewhat helpful for an unhappy patient. But there is surprisingly little research regarding the efficacy of antidepressants for subthreshold depression, though there appears to be a small benefit of medications for “mild” depression (patients who met diagnostic criteria but had relatively mild symptom severity) (Fournier JC et al, JAMA 2010;303(1):47– 53).
Therefore, it was nice to see a recent meta-analysis focusing specifically on patients with subthreshold depression. A total of six randomized controlled trials were included, comprising data from 234 drug-treated and 234 placebo-treated patients. There was no statistically significant benefit for antidepressants on the Hamilton Rating Scale for Depression (HAM-D) or other measures of treatment response. In the studies that used the HAM-D, patients receiving medication were less than one point better off than those receiving placebo. Response rates were 41% for patients on antidepressants and 38% for placebo patients (Barbui C et al, Br J Psychiatry 2011;198:11–16).
TCPR’s Take: Though both the number of included studies and the number of patients was small, the results were quite consistent across trials—so it seems that antidepressants are probably ineffective for subthreshold depression. Does this mean we should turn to therapy for these patients? A meta-analysis of seven studies including 700 total patients with subthreshold depression found that psychotherapy was more effective than treatment as usual (TAU) (Cuijpers P et al, Acta Psychiatr Scand 2007;115(6):434–41). However, TAU was not always clearly described in these studies, and in some cases it consisted of no treatment. Thus, we can be sure that psychotherapy works better than no treatment or very minimal treatment for subthreshold depression, but no study has directly compared psychotherapy with medication for these patients. So we can cautiously recommend psychotherapy to patients with subthreshold depression, but more research is needed.
Are Depot Antipsychotics More Effective than Oral Meds? Maybe
Clinical folklore (and occasional drug reps) have suggested that depot antipsychotics have adherence advantages over their oral counterparts. In TCPR, December 2010, we reviewed this topic and found little solid evidence that depots reliably enhance patient adherence.
A recent meta-analysis of 10 comparative trials, including 1,700 patients, examined how the two types of medication compared at reducing relapse in schizophrenia. Only studies on outpatients with at least a one-year follow-up were included.
Depot medications included: fluphenazine (Prolixin; six trials); risperidone (Risperdal Consta; two trials); haloperidol decanoate (Haldol; one trial), and zuclopenthixol (Clopixol; one trial). Oral drugs included: Prolixin (four trials); pimozide (Orap; two trials); Clopixol (one trial); quetiapine (Seroquel; one trial); olanzapine (Zyprexa; one trial); and any injectable antipsychotic (one trial).
Patients on depot medication had a lower relapse rate: 21.6% vs 33.3% for those on oral drugs. However, rehospitalization rates were not significantly different: 13.7% for depot vs 18.6% for oral.
Dropout rates were similar in the two groups: 54% depot and 59.8% oral. Significantly fewer patients on depot meds dropped out due to lack of treatment efficacy: 20.6% vs 29.6% (Leucht C et al, Schizophr Res; online ahead of print).
TCPR’s Take: At first glance, the results slightly favor depot medications. But the authors noted several caveats. Half of the included studies used different drugs in the oral and depot groups. However, when examining only studies that compared the same drug, patients on depot had a lower rehospitalization rate than patients on oral medication. Other methodological issues: only half of the studies were double-blind; studies varied notably in their definition of relapse; some studies excluded non-adherent patients; and, based on an email exchange with Dr. Leucht, drug companies either sponsored or provided the medications for a number of the studies reviewed. Depot antipsychotics appear to have a slight advantage over orals in preventing relapse, but the difference is small, and this result is based on varying studies with different methodologies. We recommend prescribing depot meds judiciously, based on a good conversation with your patients.