PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Stroke. Author manuscript; available in PMC 2012 November 1.
Published in final edited form as:
PMCID: PMC3223021
NIHMSID: NIHMS320217

Increased frequency of first episode poststroke depression following discontinuation of escitalopram

Katsunaka Mikami, M.D., Ph.D.,1,6 Ricardo E. Jorge, M.D.,1 David J. Moser, Ph.D.,1 Stephan Arndt, Ph.D.,1 Mijin Jang, M.S.,1 Ana Solodkin, Ph.D.,2 Steven L. Small, Ph.D., M.D.,3 Pasquale Fonzetti, M.D.,4 Mark T. Hegel, Ph.D.,5 and Robert G. Robinson, M.D.1

Abstract

Background and Purpose

To compare escitalopram, problem-solving therapy (PST), and placebo, to prevent poststroke depression during 6 months after discontinuation of treatment.

Methods

We examined for depression, 33 patients assigned to placebo, 34 to escitalopram, and 41 to PST.

Results

After controlling for age, gender, prior mood disorder, and severity of stroke, new onset major depression and Hamilton Depression scores were significantly higher 6 months after escitalopram was discontinued, compared to the PST or placebo groups.

Conclusions

Discontinuation of escitalopram may increase poststroke depressive symptoms.

Keywords: stroke, depression

We previously reported that non-depressed patients given placebo over 1 year following stroke were 4.5 times more likely to develop new onset depression than patients given escitalopram and 2.2 times more likely than patients given PST.1

In the current study, we examined the frequency of major depression and changes in Hamilton Depression Rating Scale (HDRS)2 in this population 6 months following discontinuation of treatment. We hypothesized the preventive benefit of escitalopram and PST compared to placebo would continue after cessation.

Patients and Methods

The patient population was described in detail in prior publications. 1 Non-depressed patients age 50 to 90 were enrolled within 3 months of an index stroke, from The University of Iowa, the University of Chicago, and Burke Rehabilitation Hospital.

In a randomized controlled design, patients were assigned for 12 months to escitalopram (10 mg/d ≥65 years; 5 mg/d >65 years), placebo, or PST. The PST, developed for treating medically ill patients with depression,3 consisted of 12 sessions in which the patient selected a problem and used a 7-step process to arrive at a course of action.

Using the Structured Clinical Interview for DSM-IV diagnosis (SCID)4 and the HDRS, 2 patients were assessed for major depression and its severity 6 months after cessation of treatment. Secondary outcome measures included activities of daily living using the Functional Independence Measure (FIM).5

Escitalopram, PST, and placebo groups were compared using Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. Changes in HDRS were compared using a linear regression model with covariates of age, gender, prior history of mood disorder, treatment received (escitalopram versus non-escitalopram), and FIM at 12 months since we assumed these variables might influence the HDRS during the 6-month follow-up.

Results

A total of 33 patients randomized to placebo, 34 to escitalopram, and 41 to PST were examined 6 months after cessation. Baseline characteristics showed no significant intergroup differences (Table 1). Frequency of major depression was 4 cases for escitalopram (11.8%) versus 0 for placebo (Fisher’s exact test; P=0.1139), and 0 for PST (Fisher’s exact test; P=0.0382).

Table 1
Baseline characteristics of poststroke patients in the placebo, escitalopram, or problem-solving therapy groups

The escitalopram group showed significantly increased HDRS scores only at 18 months (Kruskal-Wallis test; χ2 (2), 10.05; P=0.0066) (Table 2). Alinear regression model covaried for age, gender, prior history of mood disorder, escitalopram versus non-escitalopram, and severity of stroke as measured by FIM at 12 months showed a beta coefficient for change in HDRS for “escitalopram versus non-escitalopram” of 1.87 (95% CI, 0.41–3.32; P=0.0125). There was no effect of treatment on change in FIM score (beta-0.64, 95% CI 2.23–0.94, p=0.42).

Table 2
Scores of HDRS, FIM and SFE at Baseline, 12 months and 18 months

Discussion and Summary

This study found that non-depressed stroke patients, who discontinued escitalopram after 12 months, were more likely to develop major depression and increased HDRS scores during the next 6 months than patients given placebo or PST.

This study is limited by not including acute stroke patients such as those with severe co-morbid illness. Furthermore, the number of new major depressions were relatively small. Thus, our findings should be considered preliminary.

For clinicians, the most important implication of our finding is that patients, given antidepressants following stroke, may be more prone to develop depressive symptoms than untreated patients once their antidepressants are stopped. They may need to be monitored for depression for at least 6 months. Furthermore, treatment for longer than 1 year may be needed or slow tapering of antidepressants. Since PST effectively prevented poststroke depression and no new depressions occurred after cessation, should PST be the first treatment? Perhaps, but the lack of general availability of PST and administration of 12 therapy sessions will probably limit its use.

Cessation of escitalopram may have led to increased depressive symptoms because drugs like escitalopram produce changes in enzymes involved in synthesis and metabolism of biogenic amines and receptors and neuroplastic changes in hippocampus and prefrontal cortex.6, 7 Abrupt withdrawal of escitalopram may have led to neural system dysfunction and depression. Increased depressive symptoms after cessation of antidepressants has been reported in other studies. 8,9 It is important to remember that antidepressants may improve cognitive10 and physical recovery11 following stroke.

Acknowledgments

Sources of Funding

This work was supported in part by NIH grant R01 MH065134 (RGR).

Footnotes

Disclosures

Drs. Jorge and Robinson are consultants for Avanir Pharmaceutical. Dr. Small, editor for Brain and Language, receives compensation from Elsevier. Drs. Arndt, Mikami, Moser, Solodkin, Fonzetti, Hegel and Ms. Jang have no disclosures.

Clinical Trial Registration Information

Clinicaltrials.gov identifier: NCT00071643

References

1. Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: A randomized controlled trial. JAMA. 2008;299:2391–2400. [PMC free article] [PubMed]
2. Hamilton MA. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62. [PMC free article] [PubMed]
3. Mynors-Wallis LM, Gath DH, Lloyd-Thomas AR, Tomlinson D. Randomised controlled trial comparing problem solving treatment with amitryptyline and placebo for major depression in primary care. BMJ. 1995;310:441–445. [PMC free article] [PubMed]
4. Spitzer RL, Williams JBW, Gibbon M. Structured clinical interview for dsm-iv (scid) New York: Biometric Research, New York State Psychiatric Institute; 1995.
5. Forer S, Granger CV. Functional independence measure. Buffalo, NY: The Buffalo General Hospital State University of New York at Buffalo; 1987.
6. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805–809. [PubMed]
7. Castren E, Rantamaki T. The role of bdnf and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity. Dev Neurobiol. 2010;70:289–297. [PubMed]
8. Baldessarini RJ, Tondo L, Ghiani C, Lepri B. Illness risk following rapid versus gradual discontinuation of antidepressants. Am J Psychiatry. 2010;167:934–941. [PubMed]
9. Narushima K, Kosier JT, Robinson RG. Preventing poststroke depression: A 12-week double-blind randomized treatment trial and 21-month follow-up. J Nerv Ment Dis. 2002;190:296–303. [PubMed]
10. Jorge RE, Robinson RG. Escitalopram enhances cognitive recovery following stroke. Arch Gen Psychiatry. 2010;67:187–196. [PMC free article] [PubMed]
11. Mikami K, Jorge RE, Adams HP, Jr, Davis PH, Leira EC, Jang M, et al. Effect of antidepressants on the course of disability following stroke. Am J Geriatr Psychiatry. 2011 in press. [PMC free article] [PubMed]