Opioid Maintenance Therapy: A Review of Methadone, Buprenorphine, and Naltrexone Treatments for Opioid Use Disorder.

The rates of opioid use and opioid related deaths are escalating in the United States. Despite this, evidence-based treatments for Opioid Use Disorder are underutilized. There are three medications FDA approved for treatment of Opioid Use Disorder: Methadone, Buprenorphine, and Naltrexone. This article reviews the history, criteria, and mechanisms associated with Opioid Use Disorder. Pertinent pharmacology considerations, treatment strategies, efficacy, safety, and challenges of Methadone, Buprenorphine, and Naltrexone are outlined. Lastly, a practical decision making algorithm is discussed to address pertinent psychiatric and medical comorbidities when prescribing pharmacology for Opioid Use Disorder.

The Interaction Between Brain-Derived Neurotrophic Factor Levels and Alcohol Consumption, Sleep Disturbance and Sex-Hormones in Alcohol Use Disorders.

AIMS: Brain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors. METHODS: Data from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model. RESULTS: No significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = -0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found. CONCLUSION: Our study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker.

Assessing the quality of publicly available videos on MDMA-assisted psychotherapy for PTSD.

BACKGROUND AND OBJECTIVES: Patients increasingly rely on the Internet for healthcare information. This study aimed to evaluate the quality of videos on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder (PTSD) on YouTube™. METHODS: YouTube™ was searched for the terms "MDMA" and "PTSD." The 100 most viewed videos were analyzed using three standard quality measures: Global Quality Scores (GQS), JAMA benchmark, and DISCERN. Viewer engagement features and source of upload, video duration, inclusion of patient narrative and/or MD/DO/PhD, the mention of lack of Food and Drug Administration (FDA) approval, side effects, potential for abuse, and use in conjunction with psychotherapy were recorded. RESULTS: The videos were of poor quality (mean GQS: 2.26 ± 0.94/5, JAMA: 1.96 ± 0.45/4, and DISCERN: 29.5 ± 8.2/80). A significant positive association was found between video quality and duration (GQS: r = .5857, p < .0001, JAMA: r = .279, p = .0409, DISCERN: r = .5783, p < .0001). Videos including an MD/DO/PhD had the highest scores (GQS: 2.87/5 [1.22], p = .006, DISCERN: 38.35/80 [13.32], p < .0003). A minority of videos were uploaded by academic institutions (1%); most were from professional organizations (29%). No correlation was found between quality and viewer engagement features-number of views, subscribers, likes/dislikes, or comments. A majority mentioned that MDMA must be used in conjunction with psychotherapy (85%) and is not FDA-approved (82%) for PTSD. Only 32% of videos mentioned risks or potential for abuse. CONCLUSIONS: These findings highlight the need for better quality of online health material and an opportunity for involvement of healthcare professionals in the dissemination of accurate health information via content creation. SCIENTIFIC SIGNIFICANCE: This is the first study to examine publicly available information on the use of MDMA for PTSD.

Increased Patient Safety-Related Incidents Following the Transition into Daylight Savings Time.

BACKGROUND: "Spring forward," the start of daylight savings time (DST), reduces sleep opportunity by an hour. Insufficient sleep in healthcare workers resulting from the spring forward time change could potentially result in an increase in medical errors. OBJECTIVE: We examined the change in reported patient safety-related incidents (SRIs), in the week following the transition into and out of DST over a period of 8 years. DESIGN: Observational study SETTING: A US-based large healthcare organization with sites across multiple states MEASUREMENTS: Voluntarily reported SRIs that occurred 7 days prior to and following the spring and fall time changes for years 2010-2017 were ascertained. SRIs likely resulting from human error were identified separately. The changes in the number of SRIs (either all SRIs or SRIs restricted to those likely resulting from human error) from the week before and after the time change (either spring or fall) were modeled using a negative binomial mixed model with a random effect to correct for non-independent observations in consecutive weeks. RESULTS: Over the 8-year period, we observed 4.2% (95% CI: - 1.1 to 9.7%; p = 0.12) and 8.8% (95% CI: - 2.5 to 21.5%; p = 0.13) increases in overall SRIs in the 7 days following DST when compared with 7 days prior for spring and fall, respectively. By restricting to SRIs likely resulting from human errors, we observed 18.7% (95% CI: 5.6 to 33.6%; p = 0.004) and 4.9% (95% CI: - 1.3 to 11.5%; p = 0.12) increases for spring and fall, respectively. CONCLUSION: Policy makers and healthcare organizations should evaluate delayed start of shifts or other contingency measures to mitigate the increased risk of SRIs during transition to DST in spring.

Methadone-Related Delirium: Prevalence, Causes, and Outcomes.

Goals consist of determining 5-year prevalence and recurrence of methadone-related delirium (MRD), along with causes, treatments, and outcomes. Sample comprised 81 patients in methadone maintenance treatment. Criteria for MRD encompassed delirium with high methadone serum levels plus alleviation of delirium upon lowering methadone serum levels. MRD occurred in 14 cases who had 25 episodes. MRD precipitants included physician prescribing (i.e., excessive methadone or medications slowing methadone metabolism), drug misuse, and renal-fluid alterations. Social affiliation (housing with family, intimate partner) reduced MRD; employment increased MRD. Recovery occurred in 23/25 episodes of MRD; two episodes progressed to dementia. Obtaining serum methadone levels fostered prompt recognition.

PNPLA3 Association with Alcoholic Liver Disease in a Cohort of Heavy Drinkers.

AIMS: Prior studies have established variation at the PNPLA3 gene to be associated with a risk of developing alcoholic liver disease (ALD). We attempt to replicate this finding and other potential genetic variations previously associated with ALD utilizing a case-control design in a cohort of subjects with alcohol use disorders. SHORT SUMMARY: This case-control study performed in a US clinical sample of heavy drinkers, replicates the previously reported association between ALD and rs738409 polymorphism in the PNPLA3 gene in heavy drinkers. This association persisted after accounting for the subject's diabetes status. METHODS: Patients of European ancestry with a history of ALD were identified (n = 169). Controls consisted of patients without ALD who were from the same cohorts and were ≥ 30 years of age, had lifetime total years drinking ≥20 and lifetime maximum drinks per day ≥12 (n = 259). Patients were genotyped for 40 candidate single nucleotide polymorphisms (SNPs) selected for the purpose of testing their association with ALD. The association of each SNP with ALD was tested using a logistic regression model, assuming log-additive allele effects. Bonferroni correction was applied and multivariable logistic regression models were used to account for relevant covariates. RESULTS: Age, sex, and body mass index (BMI) distributions were similar between cases and controls. Diabetes was more prevalent in the ALD cases. Three SNPs were associated with ALD at the nominal significance level (rs738409 in PNPLA3, P = 0.00029; rs3741559 in AQP2, P = 0.0185; rs4290029 in NVL, P = 0.0192); only PNPLA3 rs738409 SNP was significant at the Bonferroni-corrected P-value threshold of 0.00125. Association results remained significant after adjustment for diabetes status. CONCLUSION: Our case-control study confirmed that PNPLA3 rs738409 SNP is associated with ALD. This is an important replication in a US clinical sample with control subjects who had long histories of alcohol consumption.

The association between sleep disturbances and alcohol relapse: A 12-month observational cohort study.

BACKGROUND: Sleep disturbances are extremely common in alcohol recovery. Systematic research into the relationship between alcohol relapse and sleep disturbances using validated scales and accounting for potential confounders is lacking. METHODS: Patients admitted to a 1-month residential addiction treatment program were administered the Pittsburg Sleep Quality Index (PSQI) at admission/discharge. In addition, the Alcohol Use Disorders Identification Test (AUDIT), Patient Health Questionnaire-9 (PHQ-9), and Pennsylvania Alcohol Craving Scale (PACS) were administered. Patients were contacted every 3 months over 1 year following discharge. Associations of clinical factors with time until relapse were examined using univariate Cox proportional hazard models. RESULTS: One-hundred and nineteen patients with alcohol use disorders met inclusion criteria (mean age 50.6 ± 13.2 years, 57% male), relapse data were available for 81 patients. Eighty percent of subjects had other psychiatric diagnoses, 66.3% had sleep disturbances at the time of admission, and 57.1% were using hypnotics; 49.1% of patients had sleep disturbances at discharge. Sleep disturbances at admission and discharge were not associated with alcohol relapse at 12 months (OR = 1.00, 95% CI = 0.89-1.13; p = 0.95 and OR = 0.97, 95% CI = 0.86-1.09; p = 0.61). The PSQI sub-scale scores were also not associated with relapse at 12 months. The use of alcohol to help fall asleep (OR = 3.26, 95% CI = 1.33-7.95; p = 0.008), hypnotic use at admission (OR = 4.03, 95% CI = 1.63-9.97; p = 0.002) and age (OR = 1.03, 95% CI = 1.00-1.06; p = 0.035) were associated with relapse over 12 months. CONCLUSION: In patients completing a residential treatment program, sleep disturbances as measured by the PSQI were not associated with alcohol relapse at 12 months. Alcohol use as a hypnotic and hypnotic use at admission were associated with subsequent relapse.

The course of sleep disturbances in early alcohol recovery: an observational cohort study.

INTRODUCTION: Understanding the course and determinants of sleep disturbances in alcoholic patients may help identify patients at high risk of persistent sleep problems, relapse and guide treatment interventions. METHODS: We prospectively administered the Pittsburgh Sleep Quality Index (PSQI) to all patients (N = 196) admitted to a 1-month residential treatment program. Our analysis excluded patients with active drug abuse/dependence. Demographic data, psychiatric diagnoses, Patient Health Questionnaire-9 (PHQ-9), Alcohol Use Disorders Identification Test (AUDIT) and Inventory of Drug Taking Situations (IDTS) scores were obtained. Univariate and logistic regression analyses were performed using sex, age, hazardous alcohol use, PHQ-9 scores, hypnotic use, and use of alcohol as a hypnotic as correlates to admission PSQI scores and improvement in PSQI scores. RESULTS: A total of 119 alcoholic patients met inclusion criteria (mean age 50.6 ± 13.2 years). The rates of sleep disturbances at admission and discharge were 69.3% and 49.1%, respectively. Self report of using alcohol to fall asleep and use of hypnotics were associated with elevated PSQI scores. Total PSQI scores improved over 4 weeks (p < .001). Change in PSQI scores was not effected by gender, use of hypnotics, hazardous alcohol use, use of alcohol as a hypnotic or co-morbid psychiatric diagnosis. Older age predicted improvement in PSQI scores in patients with sleep disturbances (p = .004). CONCLUSION: While a large proportion of alcoholics had sleep disturbances upon admission and at discharge from a residential treatment program, only older age was associated with improvements in sleep disturbances during early alcohol recovery.

Correlates to Improvement in Sleep Duration in Acute Mania and Depression.

Objective: To examine sleep duration at admission and discharge and change in sleep duration during hospitalization in patients experiencing a manic episode and compare these parameters to patients hospitalized for major depressive disorder (MDD) during the same time frame. The correlation between sleep duration parameters in those with mania and MDD with length of hospital stay, after accounting for possible confounders, was also examined.Methods: This retrospective study examined patients admitted to an acute care psychiatric unit from 2018 to 2021 with an episode of mania or MDD. Sleep duration was determined based on nursing observer report.Results: The study included 41 patients with mania (32.9 ± 1.7 years) and 38 patients with MDD (32.7 ± 1.8 years). Mania patients had longer hospitalization and received higher antipsychotic and benzodiazepine doses, but fewer hypnotics (all P < .005). No differences were found in sleep duration at admission (P = .109) and discharge (P = .623) in the mania and MDD groups. Change in sleep duration was 1.14 ± 0.27 and 0.37 ± 0.28 hours (P = .05) in the groups, respectively. In those with mania, sleep duration at admission negatively correlated with length of stay (r = -0.033; P = .03). Sleep duration parameters were not correlated with length of stay in patients with MDD.Conclusion: There was a trend toward greater improvement in sleep duration in inpatients with mania versus MDD. Sleep duration at admission correlated with length of hospitalization in patients with mania. Future studies should examine whether attempts to increase sleep duration can improve patient outcomes.Prim Care Companion CNS Disord 2024;26(1):23m03620. Author affiliations are listed at the end of this article.

Clinical Utility and Impact of Phosphatidylethanol Testing in Liver Transplantation Evaluations.

BACKGROUND: Phosphatidylethanol (PEth) is a serum biomarker that can detect alcohol use within the last 28 days with excellent sensitivity and specificity. Urinary ethyl glucuronide (uEtG) is commonly used in transplant settings to screen for alcohol use; however, it has several limitations relevant to liver transplantation. Transplant centers are beginning to regularly utilize PEth as part of the screening process for high-risk liver transplantation candidates although the clinical utility of uniform pre-transplant PEth testing is unclear. METHODS: This was a retrospective chart review of all patients evaluated for liver transplantation from December 1, 2019, through May 31, 2022, at a large academic tertiary referral center utilizing uniform serum PEth and uEtG screening. Information regarding the patients' transplantation status, age, sex, race, Model for End-Stage Liver Disease score, and PEth levels was obtained. In those with a positive PEth, we examined if the result would have been detected with uEtG, identified a discrepancy from the documented patient report of last use, led to a change in the Psychosocial Assessment of Candidate for Transplantation score, or influenced the transplant selection committee's decision. RESULTS: Our sample included 865 individuals (mean age = 55.20, 61.27% male and 82.54% white) with calculated Model for End-Stage Liver Disease-Sodium scores ranging from 6.43 to 50.65 (mean: 18.09; median: 16.46). Forty-eight patients were found to have a positive PEth (PEth range 20-1833); 75% of the sample had alcohol-associated liver disease. In 23 of 48 (47.91%) cases, the positive PEth identified alcohol use missed by a concomitant uEtG screen. A positive PEth test identified a discrepancy from patients' self-report in 29 (60.42%) cases and influenced the selection committee's decision in 28 cases (58.33%). CONCLUSION: Uniform pretransplant PEth screening of liver transplant candidates at the time of initial evaluation identified alcohol use that would have been missed by uEtG testing, identified discrepancies from the patient's self-report, and influenced clinical decision-making in a significant number of cases. These findings support the use of uniform PEth screening in liver transplantation evaluations.

Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

The aim of this study was to assess age- and sex-related differences in multiple sleep latency test (MSLT) results and in the performance of the Epworth Sleepiness Scale (ESS) at classifying objective hypersomnia (mean sleep latency (MSL) ≤ 8 min). We studied 480 consecutive adults (39.3 ± 15.3 years old [18-93], 67.7% female) who underwent hypersomnia evaluation. We fit linear regression models to investigate associations between age and sex and sleep latencies (mean and for every nap), after adjusting for total sleep time and sleep efficiency (on polysomnography), and REM-suppressing antidepressant effect. A logistic regression was performed to assess whether age and sex were associated with sleep-onset REM period (SOREMP) occurrence. ROC analysis assessed the diagnostic performance of ESS scores to identify a MSL ≤ 8 min in different age/sex groups. For every 10 years of age, there was 0.41 (95% CI 0.11-0.72, p = 0.008) min reduction in MSL. Objectively (MSL ≤ 8 min) sleepy patients had shortening of latencies in naps 4 and 5 with aging. Female sex was associated with a higher MSL only in patients with MSL > 8 min. A 2.4% reduction in the odds of SOREMP occurrence was observed for every year of age in objectively sleepy patients (p = 0.045). ESS scores had a better diagnostic performance in older (≥ 50 years old) men than younger (< 50 years old) women (p < 0.05). Older patients with objectively confirmed hypersomnia may be sleepier in later naps, possibly due to less restorative naps and/or circadian rhythm factors. Self-reported sleepiness is more predictive of objective sleepiness in older men than younger women.

Correction: Aging and sex are associated with multiple sleep latency test findings and their relationship with self-reported sleepiness.

[This corrects the article DOI: 10.1007/s41105-024-00512-5.].

Prevalence and associations of multiple hypnotic prescriptions in a clinical sample.

STUDY OBJECTIVES: We examined the prevalence of multiple hypnotic prescriptions and its association with clinical and demographic characteristics from the electronic health record (EHR) in the Mayo Clinic Biobank. METHODS: Adult participants enrolled in the Mayo Clinic Biobank with an EHR number of ≥ 1 year were included (n = 52,940). Clinical and demographic characteristics were compared between participants who were and were not prescribed any hypnotic approved for insomnia by the US Food and Drug Administration and/or trazodone and in those prescribed a single vs multiple (≥ 2) hypnotics. A phenotype-based, phenome-wide association study (PheWAS) examining associations between hypnotic prescriptions and diagnoses across the EHR was performed adjusting for demographic and other confounders. RESULTS: A total of 17,662 (33%) participants were prescribed at least 1 hypnotic and 5,331 (10%) received ≥ 2 hypnotics. Participants who were prescribed a hypnotic were more likely to be older, female, White, with a longer EHR, and a greater number of diagnostic codes (all P < .001). Those with multiple hypnotic prescriptions were more likely to be younger, female, with a longer EHR, and a greater number of diagnostic codes (all P < .001) compared with those prescribed a single hypnotic. The PheWAS revealed that participants with multiple hypnotic prescriptions had higher rates of mood disorders, anxiety disorders, suicidal ideation, restless legs syndrome, and chronic pain (all P < 1 e-10). CONCLUSIONS: Receiving multiple hypnotic prescriptions is common and associated with a greater prevalence of psychiatric, chronic pain, and sleep-related movement disorders. Future studies should examine potential genetic associations with multiple hypnotic prescriptions to personalize treatments for chronic insomnia. CITATION: Kolla BP, Mansukhani MP, Chakravorty S, Frank JA, Coombes BJ. Prevalence and associations of multiple hypnotic prescriptions in a clinical sample. J Clin Sleep Med. 2024;20(5):793-800.

Are clinical trials for insomnia recruiting real-world patients?

Recent Phase III trials of hypnotic medications that have led to Food and Drug Administration approval have severely restrictive eligibility criteria. One hundred patients referred for insomnia who received a hypnotic medication at a large tertiary referral center were identified. Data were extracted to evaluate whether these patients would be eligible to be included in any of the recent Phase III trials. Of the 100 patients identified, only 3 were eligible. Most were excluded because of a prior or concurrent trial of cognitive behavioral therapy for insomnia. If this criterion were set aside, only 12% would have been eligible to participate. The remaining top reasons for exclusion were medical comorbidities, daytime napping, and sleep apnea. These findings question the generalizability of the regulatory studies and suggest that future trials should enroll patients with less-restrictive criteria to help determine the effectiveness of these medications in real-world settings. CITATION: Golebiowski R, Mansukhani MP, Kolla BP. Are clinical trials for insomnia recruiting real-world patients? J Clin Sleep Med. 2023;19(8):1553-1555.

Prophylactic Use of Ramelteon for Delirium in Hospitalized Patients: A Systematic Review and Meta-Analyses.

BACKGROUND: Small prospective studies, case reports, as well as some randomized placebo-controlled trials and previous meta-analyses have shown that ramelteon, a melatonin agonist, may reduce the risk of developing delirium. OBJECTIVE: The goal of this systemic review and meta-analyses was to assess the current evidence supporting the use of ramelteon in delirium prevention by including data from larger (>100 subjects) and more recent trials since the most recent meta-analyses were published in 2019. There were no exclusions for trial size, age, ramelteon dose, length of treatment, or hospital setting. METHODS: Medline, Embase, PsycINFO, EBM Reviews, Scopus, and Web of Science databases were queried using the search terms delirium (with subterms including prevention and control), ramelteon, Rozerem, or melatonin receptor agonists, for English-language publications until March 16, 2021. Randomized placebo-controlled trials of hospitalized subjects receiving ramelteon for delirium prevention were included. The primary outcome of interest was delirium incidence. Odds ratios of the risk of developing incident delirium and 95% confidence intervals were calculated using a random effects model. RESULTS: A total of 177 articles were identified by the literature search. Five studies (n = 443, 53.7% male) met criteria for inclusion in the final meta-analyses. The meta-analyses of the randomized placebo-controlled trials revealed that ramelteon did not result in a reduction in the risk of incident delirium (n = 443; odds ratio = 0.49; 95% confidence interval = 0.13-1.85). A moderate degree of heterogeneity was noted among the studies (I2 = 53%). CONCLUSIONS: Current evidence suggests that ramelteon is ineffective as a prophylactic drug in reducing the incidence of delirium in hospitalized patients.

Genetic predisposition to major depressive disorder differentially impacts alcohol consumption and high-risk drinking situations in men and women with alcohol use disorder.

Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (ß = -0.16, p = 0.0012) but not in women (ß = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies.

Effects of transcranial magnetic stimulation on sleep quality and mood in patients with major depressive disorder.

STUDY OBJECTIVES: It is unknown whether sleep quality improvements after repetitive transcranial magnetic stimulation (rTMS) are inherent to the intervention or related to improvements in depressive symptoms. This retrospective study examined sleep quality in patients with major depressive disorder before and after treatment with rTMS, adjusting for age, sex, sedative-hypnotic use, number of rTMS treatments, depression severity, and changes in depressive symptoms. METHODS: Adults with major depressive disorder underwent a 6-week course of 10 Hz rTMS over the left dorsolateral prefrontal cortex. Patients completed the Patient Health Questionnaire-9 depression rating scale and the Pittsburgh Sleep Quality Index before and after treatment. To limit confounding, analysis of depressive symptoms occurred without item 3 (the sleep item) of the Patient Health Questionnaire-9. RESULTS: Twenty-one patients completed the study, with a mean (± standard deviation) baseline Pittsburgh Sleep Quality Index score of 12.0 (± 3.8), compared to 10.5 (± 4.3) posttreatment (P = .01). The mean baseline Patient Health Questionnaire-9 score without item 3 was 17.3 (± 3.0), compared to 12.2 (± 4.9) posttreatment (P = .0001). Pittsburgh Sleep Quality Index and modified Patient Health Questionnaire-9 changes were uncorrelated in nonadjusted and adjusted linear regression models and in the Spearman rank-order correlation. CONCLUSIONS: Mood and sleep quality improved independently after rTMS treatment, even after adjusting for age, sex, sedative-hypnotic use, number of rTMS treatments, and depression severity. These findings suggest that rTMS exerts direct effects on both mood and sleep in patients with major depressive disorder. CITATION: Collins AR, Cheung J, Croarkin PA, Kolla BP, Kung S. Effects of transcranial magnetic stimulation on sleep quality and mood in patients with major depressive disorder. J Clin Sleep Med. 2022;18(5):1297-1305.

The Effects of Cannabinoids on Sleep.

The use of cannabis products to help with sleep and various other medical conditions by the public has increased significantly in recent years. Withdrawal from cannabinoids can lead to sleep disturbance. Here, we describe a patient who developed significant insomnia leading to worsening anxiety, mood, and suicidal ideation in the setting of medical cannabis withdrawal, prompting presentation to the Emergency Department and inpatient admission. There is a limited evidence base for the use of cannabis products for sleep. We provide a comprehensive review evaluating the literature on the use of cannabis products on sleep, including an overview of cannabis and related psychoactive compounds, the current state of the law as it pertains to the prescribing and use of these substances, and potential side effects and drug interactions. We specifically discuss the impact of cannabis products on normal sleep and circadian sleep-wake rhythms, insomnia, excessive daytime sleepiness, sleep apnea, parasomnias, and restless legs syndrome. We also describe the effects of cannabis withdrawal on sleep and how this increases relapse to cannabis use. Most of the studies are observational but the few published randomized controlled trials are reviewed. Our comprehensive review of the effects of cannabis products on normal sleep and sleep disorders, relevant to primary care providers and other clinicians evaluating and treating patients who use these types of products, shows that cannabis products have minimal to no effects on sleep disorders and may have deleterious effects in some individuals. Further research examining the differential impact of the various types of cannabinoids that are currently available on each of these sleep disorders is required.