Study Finds Childhood Trauma Impacts Effectiveness of Antipsychotic Medications

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As psychiatric clinicians continue to understand the ways childhood trauma (CT) impacts patients, a new study examined how the type of trauma affects the symptoms experienced by patients with schizophrenia spectrum disorder (SSD) while taking antipsychotic medications (APs) over the course of a year.¹ Although previous research on the subject is scarce, the findings indicated the type of trauma experienced in childhood does have an impact on the effectiveness of APs. A better understanding of patients’ CT may help clinicians set expectations for how patients respond to AP treatment.

The first-of-its-kind study, from Nina Mørkved, PsyD, and colleagues, focused on 5 types of childhood trauma: emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. These 5 categories are frequently reported in SSDs, and CT has been connected to clinical features of SSDs, including cognitive impairments, duration of untreated psychosis, psychosis symptom severity, and treatment outcomes. In a previously published case study on the relationship between trauma and psychosis, researchers established that overlooking trauma in patients with psychosis limits potential recovery by leaving traumatic experiences untreated.²

Patient Demographics and Sourcing

Researchers studied 98 participants diagnosed with SSDs who had a history of childhood trauma, determined by the Childhood Trauma Questionnaire-Short Form. Patients were mainly recruited from inpatient and outpatient psychosis units. Patients were included if they were 18 or older, understood the native language, and scored ≥ 4 on at least one of the following items from the Positive and Negative Syndrome Scale (PANSS): delusions, hallucinatory behavior, grandiosity, suspiciousness/persecution, or unusual thought content.

The mean age of research participants was 30.9, more than half of the group were men, about one-third of the group had no lifetime exposure to APs, and a majority were diagnosed with schizophrenia via the International Classification of Diseases (ICD).

Exclusions included organic psychosis or psychosis due to psychoactive substance abuse, hypersensitivity to the active substance or any of the excipients of the study drugs, prolactin-dependent tumors, phaeochromocytoma, and concomitant use of medications that could induce torsade de pointes, use of levodopa, and known risk of narrow-angle glaucoma.

Researchers controlled for gender, age, onset age, DUP, education level, dosage of AP, previous exposure to APs, and substance use.

Of the 98 patients, 56.1% reported any moderate to severe trauma. Within each subtype, 17.5% reported physical abuse, 31.6% reported emotional abuse, 16.3% reported sexual abuse, 31.6% reported emotional neglect and 28.6% reported physical neglect. Over half of the sample, 66%, reported previous exposure to APs.

Study Execution and Procedure

Researchers randomized patients to receive treatment with orally administered aripiprazole, amisulpride, or olanzapine, and dosages were decided by the patient and psychiatrist within the following ranges: aripiprazole at 5 to 30 mg/d, amisulpride at 50 to 200 mg/d and olanzapine at 2.5 to 20 mg/d. This model was based on data from the Bergen, Stavanger, Innsbruck, Trondheim (BeSt InTro) study which examined the effectiveness of the three medications.³

Drug allocation was open to the patient and clinical team but sealed from researchers. Patients could refuse the first drug in the sequence; they were asked the reason for refusing and offered the second drug in the sequence. Random orders of the 3 study drugs were generated by computer for each participant.

The study did not have a control group as it was deemed unethical not to offer APs to SSD patients with symptoms of psychosis. The treatment was offered as a part of standard health care.

The PANSS was administered at baseline and weeks 1, 3, 6, 12, 26, 39, and 52 as follow-up points. The Child Trauma Questionnaire-Short Form was administered at the 6-week follow-up to avoid acute phases for increased validity. The SCID diagnostic interview was administered as soon as possible to determine inclusion according to diagnosis within the schizophrenic spectrum.

Results

Mørkved et al found abuse subtypes could predict psychosis symptom levels and AP effectiveness. Results showed that participants who experienced sexual abuse were more likely to display positive psychosis symptoms following AP treatment. The researchers found patients who experienced childhood sexual abuse may benefit from a more tailored treatment as well as standard AP treatment.

Patients who experienced physical or emotional neglect experienced increased symptom severity, while researchers found physical neglect had a higher influence on cognitive functioning. However, the researchers found no significant results were found for the CT subtypes on negative psychosis symptoms or overall PANSS scores.

“CT subtypes significantly predicted psychosis symptom levels and antipsychotic effectiveness in a prospective, semi-randomized, pragmatic RCT,” the authors concluded. “Childhood sexual abuse was associated with worse outcomes, especially more psychosis symptoms throughout 52 weeks of antipsychotic treatment. Further, there was an effect of physical neglect and decreased treatment effectiveness shown by increased levels of general psychopathology symptoms.These findings are important, as it shows that type of childhood trauma reported by SSDs patients could have implications for the effectiveness of antipsychotic treatment.”¹

References

1. Mørkved N, Johnsen E, Kroken RA, et al. Childhood trauma types in relation to antipsychotic effectiveness in schizophrenia spectrum disorders: a prospective, pragmatic, randomized controlled study. Psychiatry Res. 2024;341:116169.

2. Chari S, Lee E, Olson N, Hardy K. Opening Pandora’s Box: the importance of assessing and treating trauma in individuals experiencing psychosis. Published November 12, 2024. Accessed November 20, 2024. https://www.psychiatrictimes.com/view/opening-pandoras-box-the-importance-of-assessing-and-treating-trauma-in-individuals-experiencing-psychosis

3. Johnsen E, Kroken RA, Løberg EM, et al. Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial. Lancet Psychiatry. 2020;7(11):945-954.