Guidelines for choosing alternative treatment strategies following one or more disappointing efforts were presented by Joseph F. Goldberg, MD, Michael Thase, MD, and Stephen Stahl, MD, on the first afternoon of the 2024 American Psychiatric Association Annual Meeting in New York City. Dr. Goldberg opened “Iterative Psychopharmacology: How to Apply Principles of Clinical Reasoning and Decision Analysis to Everyday Practice” by clarifying that there is seldom a definitive next step following treatment failure. He outlined strategies that help with decision-making, including identifying treatment targets beyond symptoms and aligning our goals with those of the patient. He suggested seeking convergence on objectives after identifying and ranking separate features of the clinical problem, such as speed of recovery, cost, and lifestyle issues.
Goldberg distinguished between probabilistic treatments (those that extrapolate outcome data from large groups [i.e., randomized controlled clinical trials]) and deterministic treatments (that are effective but based only on one patient’s outcome). He encouraged listeners to continue treatments they know work for a particular patient but to be cautious about easily extrapolating their use to the next case.
Pretreatment moderators (baseline factors that inform outcome [e.g., comorbidities and demographics]) and post-treatment mediators (post-treatment issues [e.g., drug interactions, pregnancy, substance abuse, non-adherence]) must both be taken into account to find clinical success through new strategies. This leads to the concept of candidacy: the likelihood that a treatment may be safe and effective. For example, lithium carbonate would be an unlikely candidate to manage bipolar disorder in a patient with renal failure. Dr. Goldberg also encouraged developing, with the patient, a “pros and cons” list to help clarify all of these issues. This “personalized decision analytic matrix” can help frame hypotheses about the next possible interventions.
Dr. Stahl encouraged us to think dimensionally about functionalities and not restrict our concerns to lists of symptoms. He also suggested we think “two steps ahead,” as is necessary in chess. Michael Thase, MD, concluded the presentation by asking attendees to remember both how complex the brain is and how essential it is to maintain morale about treatment, suggesting that a large part of the placebo response may come from a strong and positive therapeutic alliance. He discouraged us from timidity about eliminating or “deprescribing” the least helpful medication(s) while encouraging practitioners to keep track of symptoms and adherence. Dr. Thase also stressed supporting family engagement and maintaining our clinical reasoning skills.
Goldberg and Thase supported the growing awareness that providers must be learning, identifying, and increasingly applying metacognitive skills to help overcome a high degree of treatment failure in our specialty, which is so often — unfortunately — mislabeled treatment resistance. “Thinking about how we think” helps develop a logical progression of treatment options and increases our chances of success, rather than unconsciously submitting to the irrational distortions of probability that our minds are prone to rely on.
Many providers do not feel the opportunity that more experienced psychiatrists might have of being able to “shoot from the hip” or prescribe “by the seat of (their) pants.” Intuition developed over years of clinical experience often guides experts through diagnostic and treatment decisions but can also be misdirected care due to the narrowed mindset experts commonly develop.
Stahl’s prediction — that our metacognitive skills will soon be replaced by an app — misrepresents the state and capabilities of artificial intelligence. Our responsibility is to offer our patients only our best problem-solving skills, which most of us need to improve to begin to reverse the current rate of 20-60% treatment failure. Stahl is accurate in that we must understand the data on which we base our treatment recommendations, be creative, and not be timid to try new things. As Goldberg said, we must remain focused on outcome data from the individual patient and large groups. We make errors in judgment when we extrapolate across levels of complexity, ignoring emergent properties and their contributions to results, as with expecting a single synaptic effect to be able to accurately predict clinical outcomes.
A treatment may be safe and effective for a single patient, but, as Goldberg cautions, it is not an indication to generalize the option to all patients. Well-developed and practiced metacognition, looking at all the data and prioritizing shared goals, can help us determine better ways forward by “thinking about our thinking.”
Dr. Putman declared financial relations with the APA.
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