Journal of Clinical Psychiatry最新文献

Objective: Treatment-resistant depression (TRD) affects one-third of patients with major depressive disorder, leading to increased morbidity, health care costs, and suicide risk. TRD lacks a standardized definition, complicating treatment selection. Current guidelines often group treatments broadly without clear prioritization, and evidence gaps persist, particularly regarding newer interventions and real-world clinical complexity. A simulated case-based discussion, modeling a modified Delphi consensus, was conducted to offer a clinical perspective to this gap.

Participants: A panel of 10 psychiatrists, directly engaged in the treatment of TRD at the Mayo Clinic Depression Center, participated in the surveys.

Evidence: Results represent expert opinion from participants. The process included an initial group review of TRD, where participants reviewed and presented a summary on each TRD treatment option, followed by discussion.

Process: Using a structured clinical vignette of a patient with TRD after 3 antidepressant trials, statements regarding next-step treatments were created through iterative ranking of options. Six vignette variations reflecting common clinical considerations (eg, metabolic disease, age) were included. Agreement was measured in 3 anonymous survey rounds, with group discussions in between.

Conclusions: Strong consensus emerged recommending augmentation with second-generation antipsychotics, transcranial magnetic stimulation, and ketamine/ esketamine as next-step treatments in the base vignette. Treatment preferences shifted to include nonaugmentative antidepressants and electroconvulsive therapy based on changes in patient characteristics. This study highlights the importance of tailoring treatment strategies for TRD to patient factors that extend beyond conventional guideline tiers. Integrating multidisciplinary perspectives and patient preferences holds promise for enhancing therapeutic selection and advancing personalized care in TRD.

Background: During the past 2 decades, there has been intense interest in the clinical significance of the concurrence of manic symptoms in depressed patients. DSM-5 introduced a mixed features specifier for both bipolar depression and major depressive disorder. Studies of the DSM-5 mixed features specifier have generally found a low prevalence of mixed depression. One approach toward increasing the sensitivity of the DSM-5 mixed features criteria is to lower the classification threshold. In the present study, we examine the impact of lowering the DSM-5 diagnostic threshold from 3 to 2 criteria on the prevalence and validity of the DSM-5 mixed features specifier for depression.

Methods: Four hundred fifty-nine psychiatric patients in a depressive episode were interviewed by a trained diagnostic rater who administered semistructured interviews including the DSM-5 Mixed Features Specifier Interview. The patients were rated on clinician rating scales of depression, anxiety, and irritability and measures of psychosocial functioning, suicidality, and family history of bipolar disorder.

Results: When the DSM-5 diagnostic threshold was lowered from 3 to 2 symptoms, the prevalence of mixed features based on the DSM-5 majority of episode time frame tripled from 3.9% to 13.1% (n=60). Based on a past week time frame, the prevalence of mixed features more than doubled from 9.4% to 22.9% (n=105) upon lowering the threshold from 3 to 2 criteria. However, there was no difference between the patients with 2 mixed features and patients with 0 or 1 mixed features on family history of bipolar disorder, psychosocial impairment, presence of comorbid disorders, age of onset, or history of suicide attempts or psychiatric hospitalization.

Conclusions: The results of the present study do not support lowering the DSM-5-TR diagnostic threshold for the mixed features specifier in depressed patients from 3 to 2 criteria.

Objective: To examine regional differences in cannabis use and probable cannabis use disorder (CUD) in US veterans.

Methods: Participants (N = 2,441) were drawn from a nationally representative sample of US veterans who participated in the 2022 National Health and Resilience in Veterans Study, conducted from August 11 to September 12, 2022. Weighted estimates indicated that 85.5% reported no cannabis use, 11.6% reported cannabis use, and 2.9% screened positive for probable CUD. Chi-square tests were conducted to assess differences in cannabis use and probable CUD across 9 US Census Bureau-defined regions: New England, Middle Atlantic, East and West North Central, South Atlantic, East and West South Central, Mountain, and Pacific.

Results: Significant regional differences were observed in cannabis use and CUD across the 9 regions (χ²₁₆ = 73.33, P < .001). Veterans in the Pacific region exhibited the highest rates of cannabis use (18.6%) compared to all other regions except New England (8.2%-13.4%, Ps < .05). The Pacific region also had significantly higher rates of probable CUD (8.8%) relative to all other regions (0.7%-3.5%, Ps < .05).

Conclusion: These findings demonstrate substantial regional differences in cannabis use and probable CUD among US veterans and underscore the importance of routine screening for cannabis-related problems in health care settings serving veterans, particularly in higher-prevalence regions of the United States.

Objective: Early prognostic indicators of nonresponse to buprenorphine treatment for opioid use disorder can inform targeted efforts to improve outcomes. Opioid use in the first 2-3 weeks of treatment predicts later outcomes, yet it is unclear what frequency of opioid use confers risk. We aimed to (1) identify thresholds for the frequency of early opioid use that optimally predict later sustained use and (2) quantify associations between thresholds and continuous treatment outcomes.

Method: We used data from 2 clinical trials of buprenorphine (N=562; mean age=34 years; 38% female), which were conducted from 2006-2009 and 2007-2011. Area under the receiver operating characteristic curve analyses identified optimal thresholds for opioid frequency during the first 4 weeks in predicting sustained use during weeks 5-12 (ie, 4 consecutive weeks with an opioid-positive or missing urine drug screen). Negative binomial regressions examined associations between early nonresponse and opioid-free and retention weeks.

Results: Sustained opioid use was optimally predicted by ≥1 day of opioid use in the first 2 weeks (sensitivity=0.747; specificity=0.688; positive predictive value [PPV]=0.524; negative predictive value [NPV]=0.856) and ≥2 days of use in the first 3 weeks (sensitivity=0.649; specificity=0.810; PPV=0.611; NPV=0.834). Both thresholds were negatively associated with opioid-free and retention weeks.

Conclusions: Even very low levels of opioid use in the first 2-3 weeks of buprenorphine treatment signal risk for poor outcomes. Emphasizing abstinence or near abstinence early in treatment might help promote long-term stability. Identified thresholds can be used to identify patients who may benefit from treatment adjustments and close monitoring.

Objective: Psychiatric drug development is critical for addressing the global burden of mental illness, but the degree of recent innovation is not well understood. Prior studies have highlighted concerns over the stagnation of new therapeutic approaches, particularly compared to other medical specialties. What is the degree of innovation in psychiatric drug development?

Method: This observational study cross referenced 3 drug development databases to identify new and existing therapeutics approved for psychiatric indications between January 1, 2012, and December 31, 2024. To assess each drug's degree of innovation, the primary outcome was the proportion of drugs classified as "first-in-class" with secondary measures including US Food and Drug Administration (FDA) priority review status, orphan drug designations, inclusion on the WHO's Model List of Essential Medicines, and therapeutic benefit and clinical usefulness ratings by experts.

Results: A total of 22 new psychiatric drugs and supplemental indications were identified. Of these, 7 (31.8%) were categorized as first-in-class, 2 (9.1%) were considered an advance-in-class, and 13 (59.1%) were considered addition to-class. Three drugs (13.6%) received FDA priority review, 1 (4.5%) was designated as an orphan drug, and 0 were included on the WHO's Model List of Essential Medicines. For clinical utility, of drugs with available data, none of them received a rating of "clinically helpful," and 3/22 (13.6%) were rated "clinically not helpful."

Conclusion: Innovation in psychiatric drug development in the past 13 years was limited, with most new drugs representing incremental advances rather than groundbreaking innovations. Compared to other medical fields, psychiatric drug development appears to lag in terms of novelty and clinical impact.

Objective: To examine the effectiveness of therapist-delivered video therapy habit reversal training (HRT) in large real-world samples of children, adolescents, and adults with trichotillomania and excoriation disorder (ED).

Methods: The sample included 543 patients with trichotillomania (57 children, 75 adolescents, 411 adults) and 528 patients with ED (40 children, 46 adolescents, 442 adults). Treatment followed a protocol of weekly HRT sessions, transitioning to biweekly sessions. The Repetitive Body Focused Behavior Scale was administered at baseline, weeks 5-7, and weeks 14-16 and during maintenance periods through week 52.

Results: Mean treatment duration was 14.64±2.50 weeks (7.71±2.61 sessions) for trichotillomania and 14.54±2.69 weeks (7.73±2.68 sessions) for excoriation. At weeks 14-16, trichotillomania showed a median 33.33% severity reduction (interquartile range [IQR]=11.11%-54.55%; 44.08% achieving ≥35% reduction) with large effects (Hedges g = 1.01, 95% CI [0.88-1.14]). Excoriation showed a median 33.33% reduction (IQR=12.50%-57.14%; 48.66% achieving ≥35% reduction) with large effects (Hedges g = 1.16, 95% CI [1.02-1.30]). Improvements were maintained through week 52 (trichotillomania: g=1.51 [CI, 1.23-1.79]; excoriation: g=1.56 [1.29-1.84]). Both conditions showed improvements in depression, anxiety, and stress (g=0.22-0.29). All age groups improved, with effect sizes ranging from g=0.78-1.12 for trichotillomania and g=0.68-1.54 for excoriation.

Conclusion: This analysis shows promising evidence that therapist-delivered video therapy HRT is associated with reductions in both hair-pulling and skin-picking severity and improvements in related symptoms in a real-world setting. The large treatment effects and improvements across the lifespan for both conditions suggest this delivery format may help address barriers to accessing evidence-based care for body-focused repetitive behaviors.

Pregabalin is a gabapentinoid. It does not act on GABA receptors; rather, it inhibits calcium influx into neurons by acting on the α2δ-1 subunit of voltage-gated calcium channels. This reduces release of excitatory neurotransmitters, thereby, perhaps, explaining the sedative, anxiolytic, anticonvulsant, and other properties of the drug. Pregabalin has been approved for neuropathic pain, fibromyalgia, partial-onset seizures, and generalized anxiety disorder, and is used, off-label, for pain in many other contexts and for alcohol use disorder, pruritus, restless legs syndrome, and sleep disorders. It may also be abused. About 0.04%-0.14% of women may use pregabalin during pregnancy. This article examines outcomes of pregnancies that were exposed to pregabalin. A meta-analysis of 7 cohort studies found that, even in unadjusted analysis, pregabalin was not associated with an increased risk of major congenital malformations. This finding was confirmed in later studies; or, if the unadjusted risk was significantly elevated, it was no longer so in adjusted analysis. Many studies found that anytime gestational exposure to pregabalin was not associated with a significantly elevated risk of other important birth outcomes such as stillbirth, low birth weight, preterm birth, small for gestational age, low Apgar score, and microcephaly; or the risks were elevated before but not after adjustment for covariates and confounds; or the risks were not significant relative to disease controls. Similarly, studies found that anytime gestational exposure to pregabalin was associated with no increase in risk, or with a significantly increased risk of attention-deficit/ hyperactivity disorder and related disorders, autism spectrum disorder and related disorders, and intellectual disability before but not after adjustment for covariates and confounds. As a limitation, pregabalin-exposed pregnancy sample sizes were small in all studies. On the positive side, safety impressions were obtained despite negligible adjustment for genetic, illness behavior, and environmental confounds.