New Study Finds Quetiapine More Effective Than Lithium in Reducing Treatment-Resistant Depression Symptoms
Quetiapine may be more clinically effective than lithium as an augmentation option for reducing symptoms of treatment-resistant depression (TRD), a type of major depressive disorder (MDD), according to a study published in The Lancet Psychiatry.
The pragmatic parallel-group study sought to compare the long-term clinical efficacy and cost effectiveness of the 2 medications.
“Lithium and quetiapine are first-line augmentation options for treatment-resistant depression; however, few studies have compared them directly, and none for longer than 8 weeks,” wrote Anthony J Cleare, PhD, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK, and co-authors.
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The trial’s 212 participants were recruited from 6 National Health Service trusts in England. Eligible participants included adults experiencing an active episode of MDD with a score of 14 or higher on the 17-item Hamilton Depression Rating Scale (HDRS) and an inadequate response to at least 2 antidepressant trials. Participants were randomly assigned to either receive the quetiapine (n=107) or lithium (n=105) for a 12-month treatment period. Primary outcomes included depressive symptom severity, measured by the Quick Inventory of Depressive Symptomatology (QIDS), and time to discontinue treatment.
The study found that participants taking quetiapine experienced significantly lower depressive symptom severity than those taking lithium over the 12-month treatment period (area under the between-group differences curve –68·36 [95% CI –129·95 to –6·76]; p=0·0296). While the study did not find a significant difference in the time to discontinue treatment (p=0.12), the researchers did note that quetiapine was also more cost-effective than lithium.
“Our results suggest that in routine clinical practice, quetiapine is more beneficial than lithium in reducing depressive symptoms and improving functioning in treatment-resistant depression,” the researchers wrote.
The study’s secondary outcomes included clinician-rated depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MÅDRS), and rates of response and remission. Those in the quetiapine group had significantly lower MÅDRS scores at week 52 (p=0·0435), though no significant difference was found in the response or remission rates. However, these secondary outcomes were limited by a significant amount of missing data.
The study was also limited by a lack of racial diversity, authors noted, as 89% of participants were White, and there was an imbalance in employment and gender between the 2 groups.
Further, the authors emphasized that the trial does not undermine the previously demonstrated clinical benefits of lithium for depression treatment. “There is considerable evidence that lithium is an effective treatment, and epidemiological studies suggest lithium reduces suicidality and relapse with long-term use,” they noted. “Quetiapine and lithium might have different effects on some symptoms such as sleep, appetite, and anxiety, and therefore might be suitable for different presentations of depression. An important direction for future research will be to examine predictors of treatment response to establish whether there are additional factors that might guide treatment choice, and predictors of early discontinuation, which could potentially reduce the number of unsuccessful treatment trials.”
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