When do psychiatric patients get better? Timeline and implications of clinical response to treatment in serious mental illness


Radu Mihai Paun, Alexandru Neculai Pavel, Matei Petre Valentin





One of the most important issues in clinical practice is determining if and when a treatment starts working and how long one should wait before reconsidering an unsuccessful medication trial. Prematurely switching an apparent early non-responder or maintaining an ineffective treatment for longer than necessary are two frequent and equally dangerous scenarios that can significantly prolong acute episodes and inflict additional undue suffering on patients. Finding the appropriate amount of time to wait for an improvement before pondering alterative therapeutic approaches is paramount in avoiding these pitfalls. While significant progress has been made in understanding the dynamics and implications of the response to psychotropic agents, there is still a lack of consensus regarding the application of these findings on a practical level. Most pharmacological studies use symptom scales to assess the effectiveness of a particular agent, but it is not always readily apparent how and when abstract variations in numerical score translate into concrete, visible improvements in disease severity. The aim of this review is to explore available data on the expected timeline of clinical response to treatment in patients with serious mental illness (schizophrenia, bipolar disorder, major depressive disorder) and its potential implications in optimizing clinical practice. Key points: i) Most exacerbations of schizophrenia show visible clinical improvement under neuroleptics within the first 14 days of treatment, and the absence of response at this point is highly predictive of further non-response, signaling the need for an alternative therapeutic approach, ii) Most manic episodes respond to treatment within 7 to 14 days and the absence of early improvement has been shown to be predictive of later non-response. However, a significant number of patients require longer periods to improve and the scope of available studies is relatively limited, iii) In bipolar depression the heterogeneity of therapeutic agents employed is mirrored in the varied patterns of response to treatment, iv) Most patients with unipolar depression who respond to antidepressants appear to exhibit clinical improvement within the first 14 days of treatment, with initial response being a good indicator for further response. However, because a substantial number of patients may respond slower, 4 weeks may be a more appropriate duration of time to wait before considering alternatives.


Keywords: Antipsychotic agents, antidepressant agents, schizophrenia, bipolar disorder, major depressive disorder