Journal of Clinical Psychopharmacology最新文献

Background: Lithium is a mainstay treatment for bipolar disorder, but its narrow therapeutic index and susceptibility to pharmacokinetic interactions make appropriate monitoring crucial. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are increasingly prescribed for type 2 diabetes and weight management. Scarce evidence exists on the potential interaction between semaglutide and lithium.

Methods: We present 3 cases involving patients on stable lithium regimens who were initiated on semaglutide, reviewing potential mechanisms underlying the interaction between them.

Findings: In 2 cases, lithium levels increased significantly, leading to toxicity despite stable renal function and no changes in concurrent medications. In the third case, preemptive reductions in lithium dosage mitigated toxicity, although lithium levels remained higher than anticipated. Mechanistic hypotheses that might contribute to semaglutide-associated elevated lithium levels include altered kidney function, dehydration from reduced oral intake, vomiting, or diarrhea, and delayed gastric emptying.

Conclusions: To our knowledge, this is one of the first documented case series describing a potential interaction between semaglutide and lithium in the medical literature. These cases underscore the importance of vigilant monitoring when combining lithium with semaglutide, and potentially other GLP-1 RAs. Baseline renal function, hydration status, and lithium levels should be assessed before initiating semaglutide, and lithium levels should be monitored more frequently during therapy. Clinicians prescribing semaglutide to patients on lithium should exercise caution, monitor for signs of toxicity, and provide appropriate patient education. Further research is needed to elucidate the mechanisms of this potential interaction and its clinical significance.

Background: Anticholinergic side effects from psychotropic medications are common and can lead to significant adverse events, including cognitive impairment and falls, particularly in vulnerable populations like the elderly. The cumulative anticholinergic burden from multiple medications is a critical concern associated with poorer clinical outcomes. Quantifying this burden is essential for safer prescribing.

Methods: This article developed an anticholinergic equivalence (AE) table for various psychotropic medications. Diphenhydramine (AE=1) was used as the reference standard. AE values for other drugs were derived from their M1 muscarinic receptor binding affinities (Ki) relative to diphenhydramine. This allows estimation of the diphenhydramine equivalent burden per milligram of a given medication. Antihistaminic properties were also reviewed.

Results: An AE table was generated, detailing the anticholinergic potency of numerous psychotropic agents. Values varied significantly, with older tricyclic antidepressants (eg, amitriptyline AE: 8.99) and some antipsychotics (eg, clozapine AE: 6.67, olanzapine AE: 3.08) showing high anticholinergic equivalence. Many sedating medications (eg, quetiapine, mirtazapine) are noted to have potent antihistaminic but low anticholinergic properties, clarifying that sedation is not always due to anticholinergic effects.

Conclusions: The anticholinergic equivalence table provides a practical, pharmacologically based tool for psychiatrists to quantify and compare the anticholinergic potential of psychotropic medications. This can aid in minimizing cumulative anticholinergic burden, making more informed prescribing decisions, and ultimately enhancing patient safety and therapeutic outcomes, especially in high-risk groups.

Purpose: To assess the association between prescription stimulant medication use and mortality through an analysis of data in the FDA Adverse Event Reporting System (FAERS) and of electronic health records (EHR) of adult patients at a large metropolitan health care center.

Methods: The first analysis estimated the associations between the report of a sudden death event in FAERS with stimulants (methylphenidate, dextroamphetamine, dextroamphetamine-amphetamine, and lisdexamfetamine) and with 30 medications unlikely to be associated with serious adverse cardiovascular events and sudden death (control medications); propensity score matching was used to control for confounding. The second analysis estimated the associations between all-cause mortality with stimulants and with control medications in an self-controlled case series (SCCS) of EHR data; the SCCS method assessed whether, within individuals, there was an association between initiation of stimulant medication and mortality in a subsequent risk period. Data from the FDA Adverse Event Reporting System (FAERS) and from electronic health records (EHR) of adult at a large metropolitan health care center were analyzed.

Results: In the FAERS analyses, dextroamphetamine and methylphenidate, as well as the combined stimulant class, were significantly associated with sudden death [dextroamphetamine: RR = 2.24 (95% CI: 1.37-3.65; adjusted P < 0.001); methylphenidate: RR = 2.30 (95% CI: 1.62-3.27; adjusted P < 0.001); stimulant class: RR = 2.02 (95% CI: 1.46-2.79; adjusted P < 0.001)]. In the SCCS analyses, these 2 stimulants as well as the stimulant class were significantly associated with all-cause mortality [dextroamphetamine: RR = 3.96 [95% CI: 2.07-7.56; adjusted P < 0.001); methylphenidate: RR = 4.11 (95% CI: 1.78-9.50; adjusted P < 0.001); stimulant class: RR = 3.53 (95% CI: 1.73-7.20; adjusted P < 0.001)]. In the SCCS analysis, for all stimulants except lisdexamfetamine, the RR increased with the age at first stimulant use.

Conclusions: The current results document a significant association between stimulant use and mortality and underscore existing guidance to assess current cardiovascular disease and risk factors when prescribing stimulants, especially for older adults.

Purpose/background: In 1975, US clozapine studies stopped after pharmacovigilance identified 8 Finnish fatal outcomes during agranulocytosis. In 1989, clozapine was approved with hematological monitoring for treatment-resistant schizophrenia. This study focuses on over/underrepresented fatal outcomes in female versus male adults on clozapine.

Methods/procedures: Worldwide fatal outcomes in VigiBase were included from inception to January 15, 2023. There were 6402 female adult cases and 11,222 adult male controls who were stratified by age (young, 18 to 44 years; middle-aged, 45 to 64 years; and geriatric ≥65 years). In these 6 subgroups, fatal outcomes of clozapine ADRs were ranked by frequency; over/underrepresentation was determined by comparison with corresponding male controls using univariate odds ratios (ORs), their 95% CIs and adjusted ORs (aORs) after adjusting for major confounders.

Findings/results: The unspecific label "death" accounted for around 40% of fatal outcomes. Pneumonia was the most frequent specific fatal outcome in both sexes in the middle-aged and geriatric groups. In the young group, pulmonary embolism was the most frequent specific fatal outcome in females at 8.0% (92/1147) versus 3.9% (126/3233) in males. Pulmonary embolism was overrepresented in young (adjusted OR = 2.25; 95% CI, 1.70-2.98) and in middle-aged females (aOR = 1.46, CI, 1.07-2.00). Myocardial infarction was underrepresented in young (aOR = 0.61; CI, 0.43-0.87) and in middle-aged females (aOR = 0.52; CI, 0.29-0.78).

Implications/conclusions: Young females on clozapine are at lower risk of dying from agranulocytosis, 1.7% (19/1147) than from pulmonary embolism, 8.0% (92/1147). Thus, focusing on pulmonary embolism is key to saving lives in this group. Future studies need to replicate these findings.

Purpose/background: Multiple meta-analyses have suggested that pharmacogenomic (PGx) testing may be a valuable tool to improve clinical outcomes for patients with major depressive disorder (MDD) who have failed at least one treatment. However, these meta-analyses included studies with different PGx tests and different trial designs, which produce uncertainty when interpreting results. To investigate the clinical utility of a single weighted multigene PGx test, a meta-analysis was performed for prospective studies utilizing this PGx test in adult patients with MDD.

Methods/procedures: MEDLINE/PubMed and Cochrane [including Embase, clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP)] were searched through May 2025 for studies evaluating the impact of pharmacogenomic testing on outcomes for patients with MDD. Using PRISMA guidelines, 243 records were identified, and 6 studies were included that compared PGx-guided care to unguided care in adult patients with MDD, using a single weighted multigene test.

Findings/results: Overall, 3,532 patients were included, with outcomes evaluated at week 8 or week 10. Patients with MDD whose care was guided by the weighted multigene PGx test were 30% more likely to achieve response [relative risk ratio (RR)=1.30, 95% CI: 1.16-1.47, P <0.001] and 41% more likely to achieve remission [RR=1.41, 95% CI: 1.19-1.66, P <0.001] compared to unguided care. No heterogeneity in outcomes across studies was detected.

Implications/conclusions: Prescribing informed by a weighted multigene PGx test significantly improved response and remission rates among adult patients with MDD who experienced at least 1 prior treatment failure, further demonstrating the clinical utility of weighted multigene PGx testing.

Purpose/background: Severe nausea and vomiting in pregnancy (sNVP) causes numerous detrimental short-term and long-term impacts on the physical and mental health of mothers and newborns, yet treatments are limited. When first-line drugs are ineffective, minimal data on efficacy, safety, and tolerability are available for other agents. Mirtazapine is a compelling potential therapy for sNVP because it is effective in reducing nausea and vomiting in other medically ill populations, and its safety and dosing have been established because it is prescribed to pregnant women for psychiatric disorders.

Methods/procedures: We present 2 patients with sNVP. Both had not responded to standard antiemetics recommended by the American College of Obstetricians and Gynecologists (ACOG), including third-line and fourth-line agents. They were admitted to the antepartum unit and treated with mirtazapine 15 mg orally disintegrating tablets in addition to their antiemetic regimen.

Findings/results: The symptoms of both patients rapidly improved and were sustained over a 3-week acute treatment phase without requiring dose escalation. They were tapered off other antiemetics with continued symptom control and reported minimal distress from side effects. One patient continued mirtazapine into the maintenance phase and remained symptom-free after taper.

Implications/conclusions: The outcomes from 2 carefully evaluated and tracked cases of sNVP requiring hospitalization with successful symptom resolution on mirtazapine are presented. To our knowledge, this series is the first to recommend treatment guidelines for the use of mirtazapine in the obstetric setting. We discuss how to taper and manage side effects as well as considerations for psychiatric referral. Finally, we discuss suggestions for future studies.