14: Managing Co-Occurring Mood and Substance Use Disorders With Michael J. Ostacher, MD, MPH

14: Managing Co-Occurring Mood and Substance Use Disorders With Michael J. Ostacher, MD, MPH

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sat down with Michael Ostacher, MD, MPH, to discuss managing co-occurring mood and substance use disorders (SUDs), including patient engagement, the "self-medication" narrative, and underuse of evidence-based addiction pharmacotherapy. Ostacher traced his approach to mentor Ken Minkoff, who argued against a separate addiction specialty because all clinicians treat patients with addictions. Ostacher said a directive stance with patients who use substances rarely helped, since most already recognized the problem, as opposed to something like sleep hygiene counseling, where direct instruction worked well. On whether mood symptoms or substance use came first, Ostacher said the distinction mattered less than commonly assumed, since most patients presented with continuing symptoms of both. Patients who invoked self-medication were often "precontemplative" about change, he said. Counterintuitively, in studies including STEP-BD, "the people who have substance use disorders are much more likely to get better and to get better more quickly than the people who don't have a substance use disorder and bipolar disorder," likely because motivated patients reduced use upon seeking treatment. Ostacher did not recommend avoiding addiction pharmacotherapy for bipolar patients pending disorder-specific trials. He supported varenicline and nicotine replacement for smoking cessation, methadone or buprenorphine (including long-acting injectables) for opioid use disorder, and naltrexone or acamprosate for alcohol use disorder, noting these worked regardless of psychiatric comorbidity. He cited a Stanford study in which only about 2% of patients with alcohol use disorder were discharged on an indicated medication, and a STEP-BD finding that only 4.4% of eligible bipolar patients received SUD pharmacotherapy. Ostacher said, "if you have a patient who has an alcohol use disorder diagnosis, you should offer them medications for treatment. They're welcome to not take them, but you should offer them for treatment." He added that GLP-1 agonists are being studied for alcohol use disorder. Goldberg closed by underscoring that, rather than waiting to start treatment for one condition pending resolution of the other, clinicians must address both simultaneously.

13: How AI Can Help in Everyday Psychiatry: A Conversation With Roy Perlis, MD

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Roy Perlis, MD, to discuss the role of artificial intelligence (AI) in clinical psychopharmacology, including its applications in treatment-resistant depression (TRD), suicide risk stratification, digital phenotyping, and the challenges of integrating AI tools into everyday psychiatric practice. Perlis reflected on 25 years of experience in this domain, noting that early neural network models used for psychiatry, like those applied to fluoxetine trial data, yielded little predictive signal. He observed that despite dramatic growth in dataset size—from hundreds of patients in early studies to hundreds of thousands in contemporary electronic health record (EHR) analyses—AI models have not consistently outperformed the well-trained clinician. He argued that one of AI's most practical near-term contributions is not superior prediction but rather democratization: giving the average practitioner access to the same structured clinical reasoning that expert clinicians apply intuitively. Perlis raised important concerns about the quality of the data from which AI models learn. He noted that EHR notes serve multiple purposes—clinical communication, billing, and medical-legal documentation—and that this dilutes the clinical signal in modeling cases. He warned that models can only find what clinicians document, and that key predictors of outcomes such as TRD may simply not be captured in structured or narrative data. Perlis cited his collaborative work with EHR data across institutions, noting that TRD prediction models trained at one site often fail to generalize to another, suggesting the limiting factor is data quality rather than sample size. On digital phenotyping, Perlis identified some potential, emphasizing that passively collected smartphone data (like changes in usage patterns, timing, and movement) are most informative when interpreted as deviations from an individual's own baseline rather than as population-level classifiers. He identified integration into clinical workflows as a primary barrier, not data availability or analytic methods. Perlis urged caution regarding premature deployment of AI tools, particularly suicide risk models, noting that current models still yield incorrect answers approximately 10% of the time. He also addressed large language model confabulation, clarifying that these systems are trained to complete sentences, not to acknowledge uncertainty, and that grounding models in constrained, citable data sources remains an active area of development.

12: Deprescribing: Insights From an ASCP Panel of Psychiatric Experts

Joseph F. Goldberg, MD, in this special installment of "Brain Trust: Conversations in Psychopharmacology," sat down with a panel of experts from the American Society of Clinical Psychopharmacology Annual Meeting (ASCP) Deprescribing Task Force while in attendance at the 2026 ASCP Annual Meeting in Miami, FL.  In the wake of the MAHA Institute summit on mental health on May 4, 2026, and the plans to curb “psychiatric overprescribing,” the ASCP released deprescribing recommendations for psychiatrists and practicing mental health clinicians. Goldberg has been very passionate in speaking about proper and appropriate deprescribing, as evidenced by his May 2025 cover for Psychiatric Times: “Deprescribing: Does the Term Belong in the Psychiatric Lexicon? [https://www.psychiatrictimes.com/view/deprescribing-does-the-term-belong-in-the-psychiatric-lexicon]” In this discussion, the panel explained the importance of deprescribing in the national dialogue and debate, and emphasized the need for judicious, thoughtful, supervised, purposeful, intentional, clinically-indicated decision making by clinicians. David W. Goodman, MD, highlighted the lack of understanding among a broad range of prescribers with varying degrees of training and background, leading to inaccurate diagnoses and inappropriate prescriptions.  Roger S. McIntyre, MD, FRCPC, emphasized the supply and demand mismatch in mental health services, noting the explosion in demand and the lack of quality healthcare supply.  Rajnish Mago, MD, added that the difficulty in deprescribing is due to the complexity of managing multiple medications and the reluctance of patients, families, and doctors to change treatments. Anita Clayton, MD, pointed out that most psychiatric medications are prescribed by primary care providers who lack the opportunity to follow patients closely and adjust medications as needed. Leslie L. Citrome, MD, MPH, discussed the challenges of deprescribing in primary care settings, where time limitations and lack of measurement-based care hinder effective treatment. Holly A. Swartz, MD, emphasized the importance of patient-clinician communication and the need for alternatives to medications, such as psychotherapy and lifestyle changes. Mauricio Tohen, MD, suggested that the FDA should require tapering studies for new drugs to ensure appropriate deprescribing practices. Swartz and Citrome highlighted the importance of screening tools and systematic reassessment in deprescribing. Collectively, the group discussed practical approaches to deprescribing, including starting discussions with patients and prioritizing medications based on their impact.

11: Practical Insights Into the Evolving Treatment of Bipolar Disorder With David Dunner, MD, FACPsych

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with David Dunner, MD, FACPsych, to discuss practical insights into the evolving treatment of bipolar disorder and treatment-resistant depression. Dunner described the origins of the rapid cycling concept, which emerged from his chart review of lithium nonresponders at the Columbia University lithium clinic in the early 1970s. He explained that patients with 4 or more mood episodes per year were consistently poor lithium responders, a finding later replicated and incorporated into DSM-IV. He also recounted his earlier work at the National Institute of Mental Health, where review of inpatient records led to the first characterization of bipolar II disorder: patients with hypomania and depression who did not meet criteria for full mania but demonstrated high rates of suicidality and family history of suicide. Dunner cautioned against conflating ultra-rapid cycling—which he attributed to neurological causes such as multiple sclerosis or substance use—with true bipolar rapid cycling. He also addressed the differential diagnosis of mood variability, distinguishing episodic bipolar cycling from the briefer, interpersonally triggered reactivity seen in borderline personality disorder, noting that the 2 conditions could coexist but that lithium addressed only some features of the latter. On pharmacotherapy, Dunner pointed out the commercial displacement of lithium by promoted anticonvulsants, observing that many lacked robust maintenance trial data. Regarding second-generation antipsychotics, Dunner acknowledged their efficacy as augmentation agents but noted unresolved questions about sequencing and duration of use. He emphasized neuromodulatory interventions—transcranial magnetic stimulation, vagus nerve stimulation, esketamine, and deep brain stimulation—for treatment-resistant depression. He expressed caution about psilocybin, noting that "the safety issue is more concerning to me unless they show that this is a long-term safe compound to use." On the broader state of the field, Dunner observed that mania phenotypes had shifted markedly toward mixed and dysphoric presentations. He reflected that while outcomes have improved substantially over his career, fundamental uncertainties in antidepressant selection persist: "It's clear that we lack a lot of insight into what's the absolute best drug for this patient. We're making an educated guess," he concluded.

10: The Challenge of Medication Adherence With Martha Sajatovic, MD

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Martha Sajatovic, MD, to discuss the multifaceted challenge of medication adherence in psychiatric practice. Sajatovic opened by framing adherence as behavioral and attitude alignment with a prescribed treatment plan, noting that nonadherence was far more common than most clinicians recognized. Evidence suggests that roughly half of patients prescribed psychotropic medications had difficulty maintaining recommended regimens. Sajatovic emphasized that this gap had real consequences, including relapse, hospitalization, and misattributed treatment failure—situations in which clinicians might incorrectly escalate dosing or change medications without recognizing poor adherence as the underlying cause. The discussion turned to practical strategies for initiating nonjudgmental dialogue. Sajatovic advocated normalizing adherence difficulties before asking patients whether they applied personally: “the evidence suggests that it's hard for people to stay on track with medications, and it's really common." Both Goldberg and Sajatovic agreed that the term "compliance" carried adversarial connotations and had been beneficially supplanted by "adherence," which invited shared decision-making rather than punitive evaluation. Sajatovic identified self-efficacy as an emerging correlate of better adherence, drawing on National Institutes of Health-funded research showing that patients who felt empowered to influence their own health outcomes were more likely to remain on track. Additional barriers our experts addressed included fluctuating insight in bipolar disorder, stigma, polypharmacy burden, concurrent substance use, and negative family attitudes; Sajatovic noted that in one sample group of patients with bipolar disorder, up to 40% of family members did not believe medication was indicated. Sajatovic described Customized Adherence Enhancement, a brief modular behavioral intervention she developed with colleague Jennifer Levin, MD, that targeted individualized barriers through psychoeducation, provider communication, substance-use counseling, and medication-routine strategies. The conversation concluded with a discussion of long-acting injectable antipsychotics, periodic medication reviews, and deprescribing—including a forthcoming paper by Goldberg and Sajatovic in JAMA Network Open reporting that over 90% of a Delphi expert panel endorsed regular, structured regimen reviews as standard practice.