Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.

4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1-60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

Monoamine Oxidase Inhibitors (MAOIs) in Psychiatric Practice: How to Use them Safely and Effectively.

Monoamine oxidase inhibitors (MAOIs) were among the first licensed pharmacological treatments for patients with depression but over time have fallen out of mainstream clinical use. This has led to a loss of clinician training opportunities and reduced availability of MAOIs for prescribing. This article provides a concise and practical overview of how to use MAOIs safely and effectively in psychiatric practice. We consider the history of MAOIs, why they are not used more frequently, their mechanisms of action, availability, indications and efficacy, general tolerability, withdrawal symptoms, and safety considerations (including hypertensive reactions and serotonin syndrome). Practical advice is given in terms of dietary restrictions, interactions with other medications (both prescribed and non-prescribed), and how prescribers can stop and switch MAOIs, both within the drug class and outside of it. We also provide advice on choice of MAOI and treatment sequencing. Lastly, we consider emerging directions and potential additional indications.

Psychotropic Drugs and the Microbiome.

The human gut microbiome plays a key role in host physiology in health and disease. There is a growing emphasis on the bidirectional interaction between various medications and the gut microbiome. Here, we will first review how drugs can affect microbiome composition and how the microbiome can alter the pharmacodynamics and potentially pharmacokinetics of psychotropic medications. We will take into consideration different classes of psychotropics, including antipsychotics, antidepressants, antianxiety drugs, anticonvulsants/mood stabilisers, opioid analgesics, drugs of abuse, alcohol, nicotine, and xanthines. The varying effects of these widely used medications on microorganisms are becoming apparent from in vivo and in vitro studies. This has important implications for future drug discovery in psychiatry which will need to consider the host microbiome as a major potential target.

Mental disorders, psychopharmacological treatments, and mortality in 2150 COVID-19 Spanish inpatients.

OBJECTIVE: To determine how mental disorders and psychopharmacological treatments before and during COVID-19 hospital admissions are related to mortality. METHODS: Subjects included in the study were all adult patients with a diagnosis of COVID-19, confirmed clinically and by PCR, who were admitted to a tertiary university hospital in Badalona (Spain) between March 1 and November 17, 2020. Data were extracted anonymously from computerized clinical records. RESULTS: 2,150 subjects were included, 57% males, mean age 61 years. History of mental disorders was registered in 957 (45%). Throughout admission, de novo diagnosis of mood or anxiety, stress, or adjustment disorder was made in 12% of patients without previous history. Delirium was diagnosed in 10% of cases. 1011 patients (47%) received a psychotropic prescription during admission (36% benzodiazepines, 22% antidepressants, and 21% antipsychotics). Mortality rate was 17%. Delirium during admission and history of mood disorder were independently associated with higher mortality risk (hazard ratios, 1.39 and 1.52 respectively), while previous year's treatments with anxiolytics/hypnotics and antidepressants were independently associated with lower mortality risk (hazard ratios, 0.47 and 0.43, respectively). CONCLUSION: Mental symptoms are very common in patients hospitalized for COVID-19 infection. Detecting, diagnosing, and treating them is key to determining the prognosis of the disease and functional recovery.

Long-term outcomes of psychoactive drug use in trauma patients: A multicenter patient-reported outcomes study.

INTRODUCTION: Psychoactive drug use (PDU) is reported in up to 40% of trauma patients and is associated with a higher rate of in-hospital complications. However, little is known about its long-term impact on trauma patients. We aimed to assess the long-term functional, mental, and psychosocial outcomes of PDU in trauma patients 6 to 12 months after injury. METHODS: Trauma patients with moderate to severe injuries (Injury Severity Score, >9) who had a toxicology screen upon admission to one of three level 1 trauma centers were contacted by phone 6 to 12 months postinjury. Psychoactive drug use was defined as the presence of a psychoactive, nonprescribed substance on toxicology screen including amphetamine, barbiturate, benzodiazepine, cannabinoid, methamphetamine, methadone, opioid, oxycodone, methylenedioxymethamphetamine (ecstasy), phencyclidine, tricyclic antidepressant, and cocaine. The interviews systematically evaluated functional limitations, social functioning, chronic pain, and mental health (posttraumatic stress disorder, depression, anxiety). Patients with a score of ≤47 on the Short-Form Health Survey version 2.0 social functioning subdomain were considered to have social dysfunction. Multivariable regression models were built to determine the independent association between PDU and long-term outcomes. RESULTS: Of the 1,699 eligible patients, 571 (34%) were included in the analysis, and 173 (30.3%) screened positive for PDU on admission. Patients with PDU were younger (median age [interquartile range], 43 [28-55] years vs. 66 [46-78] years, p < 0.001), had more penetrating injuries (8.7% vs. 4.3%, p = 0.036), and were less likely to have received a college education (41.3% vs. 54.5%, p = 0.004). After adjusting for patients' characteristics including the presence of a baseline psychiatric comorbidity, patients with PDU on admission were more likely to suffer from daily chronic pain, mental health disorders, and social dysfunction 6 to 12 months after injury. There was no difference in the functional limitations between patients with and without PDU. CONCLUSION: On the long term, PDU in trauma patients is strongly and independently associated with worse mental health, more chronic pain, and severe impairment in social functioning. A trauma hospitalization presents an opportunity to identify patients at risk and to mitigate the long-term impact of PDU on recovery. LEVEL OF EVIDENCE: Prognostic/epidemiologic, level III.

COVID-19 patients managed in psychiatric inpatient settings due to first-episode mental disorders in Wuhan, China: clinical characteristics, treatments, outcomes, and our experiences.

Data are scarce regarding the comorbid mental disorders and their management among COVID-19 patients. This study described the clinical characteristics and management of COVID-19 patients treated in psychiatric inpatient settings due to comorbid first-onset mental disorders in Wuhan, China. This electronic medical records-based study included 25 COVID-19 patients with first-onset mental disorders and 55 patients with first-onset mental disorders without COVID-19 (control group). Data collected included ICD-10 diagnoses of mental disorders, psychiatric and respiratory symptoms, treatments, and outcomes. Adjustment disorder (n = 11, 44.0%) and acute and transient psychotic disorders, with associated acute stress (n = 6, 24.0%) were main clinical diagnoses in the COVID-19 group while serious mental illnesses (i.e., schizophrenia, 24.5%) and alcohol use disorders (10.9%) were overrepresented in the control group. On admission, the most common psychiatric symptom in COVID-19 patients was insomnia symptoms (n = 18, 72.0%), followed by aggressive behaviors (n = 16, 64.0%), delusion (n = 10, 40.0%), and severe anxiety (n = 9, 36.0%). In addition to respiratory treatments, 76.0% COVID-19 patients received antipsychotics, 40.0% sedative-hypnotics, and 24.0% mood stabilizers. At the end of inpatient treatment, 4 (16.0%) COVID-19 patients were transferred to other hospitals to continue respiratory treatment after their psychiatric symptoms were controlled while the remaining 21 (84.0%) all recovered. Compared to the control group, COVID-19 group had significantly shorter length of hospital stay (21.2 vs. 37.4 days, P < 0.001). Adjustment disorder and acute and transient psychotic disorders are the main clinical diagnoses of COVID-19 patients managed in psychiatric inpatient settings. The short-term prognosis of these patients is good after conventional psychotropic treatment.

A simple mechanistic terminology of psychoactive drugs: a proposal.

Antidepressants, antiepileptics, mood stabilizers, and antipsychotics are extremely broadly used psychoactive drugs. These drug terms are universally used in the literature. However, the indications of these drugs have broadened substantially and overlap. The mismatch between drug classification and clinical uses causes a lot of confusion in communication and renders literature searches increasingly difficult. Therefore, we propose to drop the above terms altogether and replace them by simple mechanistic terms. Antidepressants are re-named as norepinephrine/serotonin (NE/5-HT) enhancers, antiepileptics comprising drugs with different mechanisms become neuronal inhibitors with pleiotropic effects (NIPEs), and antipsychotics become antagonists at multiple G protein-coupled receptors (mGPCR antagonists). Alkali metal ions, comprising lithium, are integrated into NIPEs. The terms "typical/first-generation/conventional" and "atypical/second-generation/non-conventional" antipsychotics should be dropped, because the original criterion for distinction, i.e., the presence and absence of extrapyramidal motor effects, respectively, is not valid anymore. The suggested changes in drug nomenclature have already been implemented into a recent textbook (Seifert R, Basic Knowledge of Pharmacology). The revised nomenclature ensures consistency with other fields of pharmacology and assignment of drug classes to indications without causing confusion. The authors acknowledge that the change in drug nomenclature is a cultural process that will take time and openly discuss the problems associated with the proposal. Ultimately, international learned societies will have to agree on a new nomenclature.

Drug trends and harm related to new psychoactive substances (NPS) in Sweden from 2010 to 2016: Experiences from the STRIDA project.

BACKGROUND: In the past decade, hundreds of new psychoactive substances (NPS) have been introduced as unclassified alternatives to the illicit drugs. The NPS represent a growing health concern by causing adverse effects and deaths but are usually undetectable by conventional drug tests. This report summarizes results and experiences from analytically confirmed drug-related acute intoxications in emergency departments (ED) and intensive care units (ICU) enrolled in the Swedish STRIDA project on NPS in 2010-2016. METHODS AND FINDINGS: ED/ICU intoxications suspected to involve NPS were enrolled in the project, after initial contact with the Poisons Information Centre (PIC). Serum/plasma and urine samples, and sometimes drug products, were subjected to a comprehensive toxicological investigation, and the PIC retrieved information on associated clinical symptoms and treatment. Between January 2010-February 2016, 2626 cases were enrolled. The patients were aged 8-71 (mean 27, median 24) years and 74% were men. Most biological samples (81%) tested positive for one, or more (70%), psychoactive drugs, including 159 NPS, other novel or uncommon substances, classical recreational and illicit drugs, and prescription medications. When first detected, most NPS or other novel substances (75%) were not banned in Sweden, but they usually disappeared upon classification, which however often took a year or longer. Some NPS were found to be especially harmful and even fatal. CONCLUSIONS: The STRIDA project provided a good overview of the current drug situation in Sweden and demonstrated a widespread use and rapid turnover of many different psychoactive substances. The accomplishment of the project can be attributed to several key factors (close collaboration between the PIC and laboratory to identify suspected poisonings, free analysis, continuous updating of analytical methods, evaluation of adverse effects, and sharing information) that are useful for future activities addressing the NPS problem. The results also illustrated how drug regulations can drive the NPS market.

20-Year Trends in the Pharmacologic Treatment of Bipolar Disorder by Psychiatrists in Outpatient Care Settings.

OBJECTIVE: Pharmacological options for treating bipolar disorder have increased over the past 20 years, with several second-generation antipsychotics receiving regulatory approval in the 1990s. The authors describe trends in use of pharmacological agents in the outpatient management of bipolar disorder. METHODS: Using nationally representative data from the 1997-2016 National Ambulatory Medical Care Surveys, the authors examined trends in the use of mood stabilizers, first- and second-generation antipsychotics, and antidepressants among psychiatrist visits for which bipolar disorder was listed among the primary diagnoses. A logistic regression model was used to identify statistically significant trends, with covariates including age, gender, race/ethnicity, and primary insurance. RESULTS: Antipsychotics were increasingly more commonly prescribed, increasing from 12.4% of outpatient visits for bipolar disorder in the 1997-2000 period to 51.4% in the 2013-2016 period (adjusted odds ratio=5.05, 95% CI=3.65-7.01). Use of mood stabilizers decreased from 62.3% of visits for bipolar disorder in the 1997-2000 period to 26.4% in the 2013-2016 period (adjusted odds ratio=0.18, 95% CI=0.13-0.27). Prescription of antidepressants occurred in 47.0% of visits for bipolar disorder in the 1997-2000 period and 57.5% in the 2013-2016 period. Prescription of an antidepressant without a mood stabilizer increased substantially, from 17.9% in the 1997-2000 period to 40.9% in the 2013-2016 period (adjusted odds ratio=2.88, 95% CI=2.06-4.03). CONCLUSIONS: Substantial changes have occurred in the treatment of bipolar disorder over the past 20 years, with second-generation antipsychotics in large measure supplanting traditional mood stabilizers. Antidepressant prescriptions persisted despite a lack of evidence for their efficacy in bipolar disorder and concerns about increasing the risk of mania. Research is needed to compare the real-world effectiveness and tolerability of newer antipsychotics with those of traditional mood stabilizers.

Evolution of Italian laws banning trafficking, use and abuse of psychotropic drugs.

The penalty system implemented by Italian law still represents a barrier against psychoactive drugs and drug addiction, especially at a time when the age of first consumption has considerably dropped. Presidential Decree n. 309 of October 9, 1990 entitled "Consolidation of the laws governing drugs and psychotropic substances, the prevention, treatment and rehabilitation of drug addicts", and referred to as Presidential Decree 309/90, is the reference text for the cultivation, production, trade and use of narcotics and other psychoactive substances in Italy. The Presidential Decree has its origins in the now-forgotten law of December 22, 1975, n. 685, amended by law 162/90, which provided a draft of the current Presidential Decree 309/90. The current text has been amended numerous times over the years.

The Psychoactive Surveillance Consortium and Analysis Network (PSCAN): the first year.

BACKGROUND AND AIMS: The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016-17). DESIGN: Observational study involving patient records and biological samples. SETTING: Seven academic emergency medical centers across the United States. PARTICIPANTS: ED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel. MEASUREMENTS: Clinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). FINDINGS: Patients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P-value < 0.05). Patients in whom synthetic cannabinoid (SC) were found (n = 27) had lower median diastolic blood pressures (70.5 versus 77 mmHg, P = 0.046) compared with the rest of the cohort. In 64 cases of single drug ingestion, benzodiazepines were administered in 25 cases and considered effective by the treating physician in 21 (84%) cases. CONCLUSIONS: During its first year of operation, the Psychoactive Surveillance Consortium and Analysis Network captured clinical data on new classes of drugs paired with biological samples over a large geographical area in the United States. Synthetic cannabinoids were the most common new psychoactive drug identified. Synthetic opioids were associated with a high rate of intubation and respiratory acidosis.

Fatalities associated with NPS stimulants in the Greater Cologne area.

This study centres on the prevalence of new psychoactive substances (NPS) stimulant use, and its relevance as a cause of death amongst individuals between the ages of 12 and 35 in the greater Cologne area. An automated solid-phase extraction-liquid chromatography-tandem mass spectrometry method was developed for the determination of 97 stimulants in urine (including conventional stimulants, e.g. amphetamine and MDMA), of which 68 analytes were fully validated for quantification. Samples of urine or kidney tissue (in cases where urine was unavailable) of 268 deceased were collected, during autopsy, between January 2011 and May 2017 and analyzed. Blood (if available) was also investigated in cases where urine/kidney samples were tested positive for NPS. An intake of stimulants (including NPS stimulants) was proven in 50 cases. In 33 cases, only conventional stimulants were detected. A total of 17 cases were tested positive for NPS. Of the 17 NPS-positive cases, 13 were also tested positive for other conventional drugs of abuse (mostly amphetamine and MDMA). In six NPS-positive cases, at least three different NPS were proven to be ingested. Due to the determined blood concentrations, NPS was assigned as the leading cause of death, or of toxicological relevance, in the cause of death in only 5 cases. In two of the cases, NPS was judged to be a component of a multidrug poisoning, but of minor relevance.

New psychoactive substances: challenges for drug surveillance, control, and public health responses.

The rapid emergence since the mid-2000s of a large and diverse range of substances originally designed as legal alternatives to more established illicit drugs (pragmatically clustered and termed new psychoactive substances; [NPS]) has challenged traditional approaches to drug monitoring, surveillance, control, and public health responses. In this section of the Series, we describe the emergence of NPS and consider opportunities for strengthening the detection, identification, and responses to future substances of concern. First, we explore the definitional complexity of the term NPS. Second, we describe the origins and drivers surrounding NPS, including motivations for use. Third, we summarise evidence on NPS availability, use, and associated harms. Finally, we use NPS as a case example to explore challenges and opportunities for future drug monitoring, surveillance, control, and public health responses. We posit that the current means of responding to emerging substances might no longer be fit for purpose in a world in which different substances can be rapidly introduced, and where people who use drugs can change preferences on the basis of market availability.

Scheduling of new psychoactive substance the Swiss way: A review and critical analysis.

Since the introduction of the European Early Warning System in 2005, >700 new psychoactive substances (NPS) have been listed. This review article presents for the first time the Swiss narcotic law in perspective of scheduling of NPS, and compares it to the regulations of the German speaking neighbours Austria and Germany. The Swiss way is a fast and effective way for scheduling NPS, with the purpose to restrict drug trafficking and for controlling the NPS drug market: the legal basis for scheduling substances of abuse is the "Law about narcotics and psychotropic substances" (BetmG, SR 812.121), which includes the "narcotic law directory (BetmVV-EDI, SR 812.121.11) suitable for listing all controlled substances. The BetmVV-EDI, SR 812.121.11 contains seven indices, with index e specifically designed for the fast scheduling of NPS. Newly appearing NPS can either be controlled under a structure analogues definition or by listing single substances. The list of single substances is updated at least once per year, and structure analogues definitions can be implemented, in order to keep track with new developments on the NPS market. The latest version from November 30th 2018 contains ten different structure analogue definitions and 207 single substances. Requirements to list NPS are their appearance on the NPS market, suspected psychotropic effects and their suggestions by Forensic professionals. As soon as substances are newly placed, on Schedule I of the 1961 Convention or Schedule II of the 1971 Convention by the Commission on Narcotic Drugs of the World Health Organization they can easily be transferred from index e to index a-d of the BetmVV-EDI, SR 812.121.11. The Austrian law uses a structure analogue and single substances approach (introduced in 2012, one update in 2016), whereas the German NPS law (established in 2016, no update yet) only lists two structure-analogue-definitions. All three legislations have defined which core structures, kinds and sites of substitutions are regulated.

Occurrence of psychiatric conditions, use of psychotropic medications and its relationship with postural balance in subjects with dizziness. / Ocorrência de condições psiquiátricas, uso de psicotrópicos e sua relação com o equilíbrio postural em sujeitos com tontura.

PURPOSE: to analyze the occurrence of psychiatric diagnosis and the use of psychotropics medications in subjects with vestibular complaints and to relate the presence of these conditions to the results of vestibulometry. METHODS: quantitative, observational, cross-sectional study with 131 patients, treated in a university hospital. They were submitted to anamnesis, visual inspection of the external ear canal, static and dynamic balance tests, Foam laser dynamic posturography and Computerized Vectoelectronystagmography. RESULTS: sample composed of 109 women and 22 men, with average age of 55 years and nine months. The most common type of dizziness was vertigo, with the presence of neurovegetative signals. A significant percentage of psychiatric complaint/diagnosis was observed, as well as the use of psychotropic medications, mainly serotonin uptake inhibitors, followed by benzodiazepines. There was a relation between the presence of psychiatric complaints with the female gender, alterations of the static balance and alterations in the Sensorial Organization Test positions III and VI. In the Vectoelectronystagmography, there was a relation between age and the presence of spontaneous nystagmus. CONCLUSION: There was a high occurrence of psychiatric complaint/diagnosis among patients with dizziness, with use of psychotropic medications substantially greater than the general population. The evaluation of postural balance revealed an association between anxiety/depression and alterations visual overload positions in the foam laser dynamic posturography. However, no relationship was found between these conditions and alterations in the Vectoelectronystagmography tests.

OBJETIVO: analisar a ocorrência do diagnóstico psiquiátrico e o uso de psicotrópicos em sujeitos com queixas vestibulares e relacionar a presença dessas condições aos resultados da vestibulometria. MÉTODO: estudo quantitativo, observacional, transversal, com 131 pacientes, atendidos em um hospital universitário. Foram submetidos à anamnese, inspeção visual do meato acústico externo, provas de equilíbrio estático e dinâmico, Posturografia dinâmica foam laser e vectoeletronistagmografia computadorizada. RESULTADOS: amostra composta por 109 mulheres e 22 homens, com média de idade de 55 anos e nove meses. O tipo de tontura mais frequente foi vertigem, com presença de sintomas neurovegetativos. Observou-se expressiva porcentagem de queixa/diagnóstico psiquiátrico, bem como uso de psicotrópicos, sendo principalmente inibidores seletivos da recaptação da serotonina, seguidos dos benzodiazepínicos. Houve relação entre a presença de condições psiquiátricas e mulheres, alterações do equilíbrio estático e alterações nas posições III e VI do Teste de Organização Sensorial. Na vectoeletronistagmografia, houve relação entre a idade e a presença de nistagmo espontâneo de olhos fechados. CONCLUSÃO: Constatou-se alta ocorrência de condições psiquiátricas entre pacientes com tontura, com uso de psicotrópicos maior que na população geral. Destaca-se a associação entre ansiedade/depressão e alterações nas posições de sobrecarga visual da posturografia dinâmica foam laser. No entanto, não foi observada relação entre essas condições e alterações nas provas da vectoeletronistagmografia.

Clinical Toxicology and Overdose of Psychiatric Medications.

This article reviews the poisoning epidemiology in Hong Kong, assessment and treatment of acute poisoning, and management of acute psychiatric medication overdose. In 2016, nearly 4000 poisoning cases involving approximately 6000 poisons were reported to Hong Kong Poison Information Centre. About 25% of the poisons involved were psychiatric-related medications. The initial medical assessment on poisoning includes history taking, vital signs monitoring, and focused physical examination. Approaches in managing acute poisoning include supportive measures, decontamination, antidote use, and enhanced elimination. Management on overdose of psychiatric medications (zopiclone, tricyclic antidepressants, selective serotonin reuptake inhibitor, antipsychotics, valproic acid, lithium, and methylphenidate) are discussed with practical tips highlighted.

Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS. METHODS: Medications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks. RESULTS: Use of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02). CONCLUSIONS: Concomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome.