Do trazodone, vilazodone, dextroamphetamine, gabapentin, melatonin, or quetiapine (Quilipta) affect cortisol and adrenocorticotropic hormone (ACTH) levels?

From the Guidelines

Trazodone, dextroamphetamine, and melatonin are the most likely to affect cortisol and adrenocorticotropic hormone (ACTH) levels among the given options, with trazodone potentially increasing cortisol levels, dextroamphetamine stimulating cortisol release, and melatonin reducing evening cortisol levels. When considering the effects of these medications on cortisol and ACTH levels, it's essential to evaluate the evidence from recent studies. However, the provided study 1 does not directly address the impact of trazodone, vilazodone, dextroamphetamine, gabapentin, melatonin, or quetiapine on cortisol and ACTH levels. Despite the lack of direct evidence, we can infer potential effects based on the mechanisms of action and known effects of similar medications.

• Trazodone, as mentioned, may increase cortisol levels, particularly during acute administration.
• Dextroamphetamine can stimulate cortisol release through its effects on the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis.
• Gabapentin generally has minimal effects on cortisol and ACTH, though some studies suggest it may slightly reduce stress-induced cortisol elevations.
• Melatonin can modulate cortisol secretion, typically reducing evening cortisol levels, which aligns with its role in circadian rhythm regulation.
• Vilazodone and quetiapine have limited evidence regarding their direct effects on cortisol and ACTH levels. These hormonal effects are generally not clinically significant for most patients taking these medications as prescribed but could be relevant for patients with adrenal disorders, those undergoing cortisol testing, or individuals experiencing stress-related symptoms. The impact on cortisol varies based on dosage, duration of treatment, individual factors, and whether the medication is taken acutely or chronically. These effects occur because many of these medications interact with neurotransmitter systems that influence the HPA axis, which controls cortisol and ACTH production, as noted in various studies, including those on the pharmacological management of related conditions 1.

From the Research

Effects of Medications on Cortisol and Adrenocorticotropic Hormone (ACTH) Levels

• The provided studies do not directly address the effects of trazodone, vilazodone, dextroamphetamine, gabapentin, melatonin, or quetiapine on cortisol and adrenocorticotropic hormone (ACTH) levels 2, 3, 4, 5, 6.
• However, it is known that some of these medications can have indirect effects on the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol and ACTH production.
• For example, trazodone has been shown to have a potential role in dementia-modifying treatment, and its effects on human cognition are complex, with both beneficial and impairing effects reported 6.
• Quetiapine is sometimes used as a first-line treatment for delirium, and its effectiveness and tolerability have been studied in various clinical settings 5.
• Gabapentin and pregabalin are used to manage postherpetic neuralgia, and their use can affect the prescription of other neuropathic pain-related medications 3.
• Melatonin and trazodone have been compared as treatments for new-onset insomnia in hospitalized adult patients, with no significant difference in the primary outcome observed 4.
• The study on corticosteroids highlights the importance of understanding their metabolic effects and the need for careful consideration of their use in clinical practice 2.

Specific Medications and Their Effects

• Trazodone: may have a dual effect on human cognition, with acute use associated with impaired cognitive function and long-term use with preventing cognitive deterioration 6.
• Quetiapine: can be a candidate drug as one of the first-line drugs for delirium, with its effectiveness and tolerability studied in various clinical settings 5.
• Gabapentin: its use can affect the prescription of other neuropathic pain-related medications, and a greater proportion of patients prescribed pregabalin attained therapeutic dose levels compared to those prescribed gabapentin 3.
• Melatonin: compared to trazodone, melatonin had a similar rate of adverse events and a lower rate of patients requiring an additional sleep aid during hospitalization 4.
• Vilazodone, dextroamphetamine: there is no direct evidence in the provided studies regarding their effects on cortisol and ACTH levels.