Lurasidone and Mood Stabilizers in Treatment-Resistant Unipolar Depression: A Case Report Study

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To the Editors
Major depression is a disabling disorder affecting about 8.2% of people yearly with a worldwide prevalence rate ranging from 10% to 19%.1 According to the STAR*D study, more than 50% of patients with depression have treatment-resistant unipolar depression (TRD),2 because they do not respond to the first antidepressant trial, using definition of TRD by Fava.3 In the last decade, the US Food and Drug administration has approved the atypical antipsychotics (AAPs) quetiapine extended-release4 and aripiprazole5 as augmentation therapy for the treatment of unipolar depression, along with the combination of olanzapine and fluoxetine.6 Thus, the use of AAPs with or without concomitant antidepressant therapy is an increasingly popular strategy for the treatment of depression. Lurasidone is a novel AAP approved by the US Food and Drug administration for the treatment of schizophrenia and bipolar I depression. However, there are no clinical data concerning the use of lurasidone in unipolar TRD.
Here, we present 4 patients diagnosed with major depressive disorder ascertained by the Structured Clinical Interview (SCID-I, SCID-II) for the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition without manic or hypomanic symptoms by the Young Mania Rating Scale (mean, 1.25 ± 0.62). These patients all had TRD; they were treated with lurasidone and mood stabilizers. Four patients (2 women and 2 men; mean age, 49.7 ± 5) from the Registry of the Mood Disorders Clinic of the McGill University Health Center were evaluated (Study 13-375-PSY, with ethical approval by the McGill University Health Center Institutional Review Board). These patients were diagnosed with TRD because they had failed an average of 6.5 ± 4 pharmacological trials with adequate antidepressant dose and duration and did not achieve any improvement [defined as <20% improvement on the Hamilton Rating Scale for Depression (HAM-D) score], including several trials with different selective serotonin reuptake inhibitors. One patient had been diagnosed with a cluster C personality disorder; a second patient had been diagnosed with a cluster A personality disorder along with a depressive episode with psychotic features. Two patients were diagnosed with metabolic disease (hypertension and hypercholesterolemia) and type 2 diabetes.
First, selective serotonin reuptake inhibitors were removed in all 4 cases, and noradrenergic antidepressants were prescribed: in 1 case, bupropion 150 mg/d,7 in another amitriptyline 12.5 mg/d, and another with duloxetine 30 mg/d. The patients tolerated these medications only at these relatively low doses, but have residual symptoms. Next, we added mood stabilizers as augmentation therapy8,9: in 1 case we added lithium (450 mg), and in 3 cases valproic acid (500 mg), reaching the plasmatic therapeutic level. However, residual symptoms of depression were still present at time T0 (HAM-D mean score, 20.7 ± 0.63; see T0 in the figure). Patients at T0 were markedly to severely depressed by the Clinical Global Impression scale (CGI; 5.25 ± 0.479). The average number of years they had spent in the current depressive episode was 6.8 ± 1.87. Global Assessment of Functioning at T0 was 53 ± 4.13. Clinical response was evaluated before treatment with lurasidone (T0), after 1 month (T1; corresponding to 6.3 ± 1.6 weeks), and after 4 months (T4; 17.5 ± 2.5 weeks) using the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Depression (HAM-D-17), and the CGI-Severity of Illness (CGI-S). Lurasidone treatment was then initiated at 20 mg/d on the first week, and then at T1 was increased to 40 mg/d. Compared with T0, at T1 there was a statistically significant decrease in depressive symptomatology by HAM-D-17 (P < 0.001) and MADRS (P = 0.017).
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