Brain Trust: Conversations in Psychopharmacology

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Psychiatric Times' very own editor in chief, John J. Miller, MD, to discuss the current state and future directions of pharmacogenetic testing.According to Goldberg, pharmacogenetics is almost like a Rorschach test in the eyes of many practitioners and patients: “It is thought to be a projective that you sort of identify in various ways. It is going to tell me things about myself. It is going to make predictions. It is going to help me guide treatment. It is going to override clinical factors, patient specific features that influence outcome, and really get to the heart of things.”Miller also shared his initial reactions to the introduction of this testing: "When pharmacogenetic testing first became available about 12 to 14 years ago, I was excited. And then, as I learned more about it, read the literature, and became aware of the institutions that exist to vet genes and whether or not they are clinically actionable, I became very frustrated by how overly adoptive pharmacogenomics has become when really the evidence base is not there. In fact, as we have learned more, it has become less evidence based in terms of clinical applications."Recently, the International Society of Psychiatric Genetics published a review article on genetics and psychiatry, and they concluded that there are 4 genes that are evidence based and actionable: CYP2D6, CYP2C19, HLA-B*1502, and HLA-A*3101."I think there is a mythology that all you have to do is do the gene testing, and you can choose a drug based on the results," shared Miller.When it comes to testing, Miller believes we need to alter the thinking around testing in psychiatry: "We are very selective, and we do it for a reason, because we have a hypothesis. Maybe there is atrophy. Maybe we have some neurological sign. It really should spark the curiosity of the clinician to think, would a test—any test, for that matter—be informative to answer a question. That is how I always think about any test in medicine."Together, Goldberg and Miller stress the importance of therapeutic drug monitoring and personalized medicine, while acknowledging the limitations and ongoing evolution of pharmacogenetic testing."We have a common goal. We want to do a test that is scientifically informative for you. If there is a test out there that I think will help us answer a question, I promise you, I will order it, but not everything comes down to a particular test, right? There are certain clinical impressions we have in medicine. How do you diagnose migraine headaches? There is no test for that. How do you diagnose your bowel syndrome or tinnitus? There is no test for that. So we look for tests to someday enhance or augment what we think is an observation that we would like some corroboration for," said Goldberg of speaking to patients about testing.Miller agreed, concluding that, "We do not want to put the car before the horse, and so let's stick to the what the experts who really know this stuff are guiding us, and then incrementally use what becomes clinically actionable or evidence based."

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Guy Goodwin, MD, to discuss the potential of psychedelics in treating depression and other mental health conditions. Goodwin, who is the chief medical officer at Compass Pathways, highlights psilocybin's ability to induce profound experiences that can lead to long-term improvements in mood and anxiety. "I got the opportunity to go full time into a new position with Compass Pathways to develop psilocybin. I'd been interested already, I'd advised a little bit on how to design the phase 2 clinical trial. At the time that I did that, I was a little pessimistic about whether there was really a future in this, because it looked quite hard to raise money and quite difficult to do the studies. There were a lot of things that seemed to me potentially difficult, but many of these obstacles have become overcome by the people at Compass. That was the beginning of a new life," Goodwin said of his research evolution in psilocybin.LSD, the first psychedelic, discovered in 1943 by Albert Hofmann,1 "was the stimulus to understanding serotonin metabolism and function, both in the brain and to a lesser extent, in the peripheral nervous system," shared Goodwin. Together, Goldberg and Goodwin evaluate the challenges of developing psilocybin, including regulatory hurdles and the need for careful clinical settings. Goodwin notes that psilocybin's effects are immediate and can be more effective than traditional treatments for some patients. They also touch on the potential for psilocybin to treat posttraumatic stress disorder (PTSD) and substance abuse, and the importance of understanding its pharmacodynamic properties and potential combinations with other drugs.For example, in an open-label, small study of 22 patients with PTSD, Goodwin and investigators saw an approximate 80% remission rate in symptoms.2 In the follow up interviews with patients, Goodwin found a few details very striking: "One is that patients can have the trauma recur—the actual index trauma can be something that recurs in the experience under the influence of psilocybin—and it seems to be something that is tolerated by the patient. They kind of find an indirect route to feeling better about the trauma."As to future directions, Goodwin believes we should start carefully: "We're advocating for very careful use. We're advocating reimbursement so that access is fair and equitable. Our objective is not to get this widest possible use of the drugs; Our objective is to get the proper use of the drugs in the right patient population."

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Holly A. Swartz, MD, to discuss evidence-based psychotherapies for mood disorders, emphasizing a nuanced approach to treating depression. If a patient prefers to start with psychotherapy, they should be given 6 to 12 weeks to see if it works before considering augmentation or switching to another modality, shared Swartz. The approach is similar to starting pharmacotherapy and considering augmentation or switching if there is no response.For less severe depression, Swartz recommends utilizing psychotherapies like cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT), as they are comparable to pharmacotherapy. For patients with severe depression, Swartz finds combining psychotherapy with antidepressants to be more effective; however, patients with severe depression alongside cognitive rigidity and melancholia may benefit more from pharmacotherapy, whereas patients with moderate depression and interpersonal or cognitive issues may benefit more from CBT or IPT."The way that I think about it is you have got to have stuff to work with in order for the treatments to be effective. We have seen that differential response to IPT and CPT," said Swartz.Additionally, patient preference significantly impacts treatment success, with those receiving their preferred treatment being 4 times more likely to respond."Getting what you think is going to help you feel better, get better actually matters a lot," said Swartz. The conversation also explores the integration of psychodynamic principles in pharmacotherapy, the role of psychotherapy in neuroplasticity, and the concept of deprescribing in psychotherapy."We always want to tailor our treatments for the individual. Some people might feel that they need a little bit less because they really get it, and they are able to use other coping strategies, whereas there may be others who struggle a bit more and need more frequent help. Our modal frequency would be monthly, with the capacity to flex that based on on patient needs and tailored treatments," concluded Swartz. 

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Roger S. McIntyre, MD, FRCPC, to discuss glucagon-like peptide-1 (GLP-1) agonists and their role in psychiatry. McIntyre highlights the transformative impact of GLP-1 agonists on weight and glucose management. GLP-1s are "truly transformative," McIntyre says, as they affect the brain in a way that suggests they are psychiatric drugs. There are currently 5 indications approved by the US Food and Drug Administration for obesity, diabetes, sleep apnea, cardiovascular disease, and kidney disease.1 While their use in psychiatry is off-label—for example, managing weight gain from antipsychotics—effects on brain plasticity, reward systems, and inflammation, suggest they have a broad range of uses in the space and mental health prescribers should be familiar with these drugs.2"There is in fact a relationship or association between obesity and type II diabetes, or impaired glucose tolerance, and its effect on the brain," said McIntyre. "When the brain is exposed to the milieu created by obesity or impaired glucose tolerance, that jeopardizes brain health that manifests in different types of neurologic and psychiatric disorders."Goldberg and McIntyre also discuss the importance of collaboration with specialists for managing complex metabolic conditions, in order "to help the patient as part of the circle of care"The future is very exciting. I'd encourage colleagues to stay tuned. We have many difficult to treat conditions in psychiatry, not just weight gain from drugs, but also cognitive impairment in schizophrenia, bipolar depression, treating anhedonia, and treating aspects of the medical problems we talked about. GLP-1s have moved into late phase development in the prevention of cognitive impairment in Alzheimer disease, the prevention of episodes in bipolar depression and schizophrenia, and other things like alcohol use disorder, smoking, and the list keeps going. These are well along in terms of development," said McIntyre.You can read more on GLP-1s and their potential as game-changers in psychiatric treatment from McIntyre in the 2025 July cover story of Psychiatric Times. Read it here.

Joseph F. Goldberg, MD, in his first installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Marlene P. Freeman, MD, to discuss the treatment of depression, selective serotonin reuptake inhibitors (SSRIs), and pregnancy. On July 21, 2025, the US Food and Drug Administration led an expert panel on SSRIs and pregnancy, in which they questioned the validity of psychiatric medication use during pregnancy."There were a lot of issues that came out of that panel discussion about the potential risks vs safety of SSRIs in pregnancy," said Goldberg. In their discussion, Goldberg and Freeman evaluate what the panel got wrong. Freeman, a leading expert in women's mental health, specifically discussed the complexities of treating psychiatric disorders during pregnancy, emphasizing the high rate of unplanned pregnancies and the risks of untreated illnesses: "Any prescriber should keep in mind that for women of reproductive potential, the rate of unplanned pregnancies in this country is about 50%. So whenever we are writing prescriptions or deciding on treatment plans, we want to keep in mind that even if a woman is not planning on becoming pregnant at the time, she might become pregnant at some time."She highlighted the need for well-controlled studies to understand the effects of SSRIs on pregnancy outcomes. Notably, SSRI use does not increase the risk of autism.  It is important to note though that a mental health disorder is also a risk factor to pregnant patients: "We know that with with all the major psychiatric disorders that have been studied across pregnancy, the disorder itself carries risk for the individual, the pregnancy outcomes postpartum, and for the baby, and ultimately for child development."Freeman also addressed the misinformation around stopping SSRIs in the third trimester and the importance of patient-centered, evidence-based care.