Distinguishing Schizophrenia From Substance-Induced Psychosis Part 2
Case Refresher
An 18-year-old college freshman presented to outpatient psychiatry after his second psychiatric hospitalization for psychosis following medication discontinuation and resumed daily cannabis use.
Although his symptoms initially raised the question of cannabis-induced psychosis, collateral history revealed a 6- to 9-month prodrome of negative symptoms—including social withdrawal, declining academic performance, reduced motivation, and impaired hygiene—suggesting an emerging schizophrenia-spectrum disorder.
After a comprehensive assessment, review of collateral information, and careful evaluation of the timeline of symptom onset, I concluded that schizophrenia was the most likely diagnosis.
The remaining challenge is determining the best long-term treatment strategy for this young patient who responded to antipsychotic therapy but struggled with adherence and medication tolerability.
Review Part 1 for more details on the case.
Previous Medication Trials:
He was started on risperidone during his first hospitalization. He took the medication for several weeks after discharge, but stopped it because he did not believe he had a psychiatric illness.
During the second hospitalization, he was started on olanzapine 10 mg nightly due to agitation. While his symptoms improved, he now complains that he has already gained 7 lbs. and feels tired throughout the day. He says olanzapine makes him feel “drugged,” and he does not want to continue taking it.
Albright Recommends:
This patient should not simply stop antipsychotic treatment, as this is not a substance-induced, brief psychotic episode. He has now had 2 hospitalizations and a prodrome of negative symptoms that predate his positive symptoms.
In schizophrenia, early intervention is important, as time is brain health; the more time patients spend in active psychosis, the worse their morbidity, mortality, functional, and suicide outcomes are. However, I needed to address his apprehension about the olanzapine, because ignoring his concerns could recreate the same cycle of medication response, side effects, nonadherence, cannabis resumption, relapse, and hospitalization.
The treatment plan, therefore, needed to be revised via shared decision-making to choose a treatment he could stay on and tolerate well.
To do so, I discussed the following options with the patient:
Psychosocial Interventions
An initial recommendation was to refer the patient to cognitive behavioral therapy for psychosis (CBTp), an effective form of psychotherapy for patients with thought disorders that may allow the patient to feel better heard and understood throughout his treatment journey.
Family engagement was also essential. I equipped his parents with resources, including the National Alliance on Mental Illness (NAMI) for education and tools to navigate newly diagnosed schizophrenia, to offer an additional layer of support to the patient.
Pharmacologic Options
I first validated the patient's concerns about olanzapine, acknowledging that although it had rapidly stabilized his symptoms, it was also causing bothersome weight gain and sedation. Using a shared decision-making approach, I reviewed several treatment options, including continuing olanzapine with dose reduction, switching to olanzapine/samidorphan to help mitigate weight gain while preserving efficacy, or transitioning to a different antipsychotic.
Given his history of medication discontinuation after his first hospitalization, I also discussed initiating a long-acting injectable (LAI) antipsychotic. I framed the LAI as a strategy to simplify treatment, improve adherence, and maintain stable medication levels rather than as a consequence of prior nonadherence. The specific agent would be selected based on prior response, tolerability, dosing schedule, and patient preference after confirming oral tolerability.
I also discussed xanomeline/trospium as a potential alternative because of its novel nondopamine mechanism of action and lower risk of movement disorders and metabolic adverse effects. Given his persistent negative symptoms, cognitive concerns, and intolerance of prior antipsychotics, I felt it was a reasonable option to consider, while counseling about gastrointestinal adverse effects, particularly nausea, and appropriate administration strategies to improve tolerability.
Finally, I considered clozapine but did not recommend it because the patient had not yet met criteria for treatment-resistant schizophrenia. Although clozapine remains the gold standard for treatment-resistant illness and has unique benefits for persistent suicidality and aggression, the patient’s short-term response to previous antipsychotic treatment did not indicate an issue of treatment-resistance.
Brittany Albright MD, MPH, is a Harvard-trained, triple board-certified psychiatrist with clinical expertise in interventional psychiatry, addiction psychiatry, and obesity medicine. She completed her adult psychiatry residency at the nation’s top ranked program, Massachusetts General Hospital and McLean Hospital and a fellowship in addiction psychiatry at the Medical University of South Carolina, where she serves as an Affiliate Assistant Professor in the Department of Psychiatry & Behavioral Sciences. Dr. Albright is the Founder and CEO of Sweetgrass Psychiatry, South Carolina’s largest physician-owned psychiatry practice with three locations.
Her research and academic work include numerous abstracts presented at national meetings and peer-reviewed manuscripts focused on innovative treatments and psychiatric education. A national speaker and consultant, she serves as President Elect of the South Carolina Psychiatric Association and holds multiple leadership roles with Psych Congress, including co-chair of Psych Congress Elevate and originator of the Private Practice Summit.
© 2026 HMP Global. All Rights Reserved.
Any views and opinions expressed above are those of the author(s) and do not necessarily reflect the views, policy, or position of the Psych Congress Network or HMP Global, their employees, and affiliates.
