Childhood Trauma and Outcomes With Lithium or Quetiapine in Outpatients With Bipolar Disorder


Does childhood trauma affect outcomes in bipolar disorder? Researchers analyzed the impact of childhood trauma on outcomes in outpatients with bipolar disorder treated with lithium or quetiapine in a randomized clinical trial.

childhood trauma




“Mrs Gee” is a 58-year-old Native American female with a history of bipolar disorder with psychotic features and posttraumatic stress disorder (PTSD) who presents to the outpatient clinic for an evaluation. She presents a clear history of past manic episodes associated with decreased need for sleep, racing thoughts, pressured speech, and impulsive behavior, most recently occurring about 4 months ago. Mrs Gee required inpatient psychiatric treatment. She endorses current depressed mood and insomnia.

In the past month, she has worsening of chronic auditory hallucinations of men who sexually abused her in the past. Sometimes the voices tell her to harm herself, which she is able to ignore, and she denies current suicidal ideation. She was violently raped at age 7, and was sexually assaulted by her uncle and several of her mother’s boyfriends as a teenager. She was also emotionally and physically abused by her mother. After discussing the risks and benefits of various medications, Mrs Gee is agreeable to a trial of quetiapine, which she has not taken previously. Quetiapine is titrated over 2 weeks to a dose of 400 mg at bedtime. She reports improved sleep and mood, and renewed interest in her hobbies, including handcrafting “dream catchers.” Over the next 6 months, she maintains euthymia and reports improved interactions with family and friends.

Childhood trauma is associated with the clinical course of bipolar disorder, including earlier age of onset, a greater number of mood episodes, psychotic symptoms, and psychiatric comorbidity.1 Furthermore, childhood trauma may also be associated with poorer response to anticonvulsants, although findings for lithium have been conflicting.2,3 There is an absence of studies of whether childhood trauma affects treatment with antipsychotics in patients with bipolar disorder.

The Current Study

Wrobel and colleagues studied the association between childhood trauma and symptomatic and functional treatment outcomes in outpatients with bipolar disorder randomized to lithium or quetiapine.4 The authors performed secondary analyses of the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study.5 Briefly, in this > 6 month trial, lithium or quetiapine were combined with adjunctive personalized treatments. In the study, 482 participants aged 18 to 62 with DSM-IV-TR bipolar I or II disorder and at least mild mood symptoms (Clinical Global Impressions [CGI] score ≥ 3) were randomized. Diagnosis was assessed with the Mini-International Neuropsychiatric Interview (MINI). Childhood trauma was assessed by clinical interview, and defined as exposure to physical, sexual, and/or emotional abuse. Symptoms were assessed with the Bipolar Inventory of Symptoms Scale (BISS) and CGI. Functional impairment was measured with the longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT).

Data at baseline were analyzed using logistic regression, based on participants with and without a history of any childhood trauma. Differences in treatment outcomes based on childhood trauma were analyzed using mixed effects and linear regression models.

Of the 482 participants in the trial, 6 were excluded due to “Other” abuse. Of the 476 included participants, 53% were exposed to at least 1 type of childhood trauma, including 49% for physical abuse, 6% for sexual abuse, and 76% for emotional abuse. Mean participant age was 39, and 59% were female. Participants with a history of trauma were likely to be female (odds ratio [OR]=2.0); have an earlier age of onset, more depressive episodes, a history of suicide attempts (OR=2.7), and history of psychiatric hospitalization; higher rates of PTSD (OR=2.9) and substance use (OR=1.5) comorbidity; and greater symptom severity and functional impairment. There was no difference in the dose of lithium (about 1000 mg) or quetiapine (about 345 mg) at week 2.

Participants with childhood trauma had significantly higher BISS and CGI scores at each study visit except the week 24 endpoint. However, there were no differences in the rate of improvement/symptom reduction in participants based on childhood trauma status. Participants with childhood trauma also had significantly higher functional impairment scores at week 12 and 24, but there were no differences in the rate of improvement/reduction of functional impairment in participants based on childhood trauma status. In secondary analyses, the pattern of findings for rates of symptomatic and functional improvement was similar when considering lithium and quetiapine, and different types of childhood trauma, separately.

Study Conclusions

The authors concluded that childhood trauma was related to several indicators of a worse clinical course and prognosis in bipolar disorder. However, rates of symptomatic and functional improvement following 6 months of treatment with lithium or quetiapine were similar regardless of childhood trauma status. Strengths of the study include investigation of the impact of childhood trauma on outcomes in a large, pragmatic clinical trial in participants with bipolar disorder. Study limitations include the absence of data on childhood trauma using a validated questionnaire, details of the trauma exposure (eg, age and frequency/duration), and the potential for recall bias by participants.

The Bottom Line

The present study found that a history of childhood trauma does not inhibit improvements in symptoms or functional impairment in outpatients with bipolar disorder treated with lithium or quetiapine.

Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.


1. Agnew-Blais J, Danese A. Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3(4):342-349.

2. Etain B, Lajnef M, Brichant-Petitjean C, et al. Childhood trauma and mixed episodes are associated with poor response to lithium in bipolar disorders. Acta Psychiatr Scand. 2017;135(4):319-327.

3. Cakir S, Tasdelen Durak R, Ozyildirim I, et al. Childhood trauma and treatment outcome in bipolar disorder. J Trauma Dissociation. 2016;17(4):397-409.

4. Wrobel AL, Köhler-Forsberg O, Sylvia LG, et al. Childhood trauma and treatment outcomes during mood-stabilising treatment with lithium or quetiapine among outpatients with bipolar disorder. Acta Psychiatr Scand. 2022;145(6):615-627.

5. Nierenberg AA, Sylvia LG, Leon AC, et al. Clinical and health outcomes initiative in comparative effectiveness for bipolar disorder (Bipolar CHOICE): a pragmatic trial of complex treatment for a complex disorder. Clin Trials. 2014;11(1):114-127.

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