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A high proportion of depressed patients fail to respond to antidepressant drug treatment. Treatment-resistant depression (TRD) is a major challenge for the psychopharmacology of mood disorders. Only in the past decade have novel treatments, including deep brain stimulation (DBS) and ketamine, been discovered that provide rapid and sometimes prolonged relief to a high proportion of TRD sufferers. In this review, we consider the current status of TRD from four perspectives: the challenge of developing an appropriate regulatory framework for novel rapidly acting antidepressants; the efficacy of non-pharmacological somatic therapies; the development of an animal model of TRD and its use to understand the neural basis of antidepressant non-response; and the potential for rapid antidepressant action from targets (such as 5-HT1A receptors) beyond the glutamate receptor.

Background Despite abundant evidence that emotional distress is frequent in cancer patients and associated with adverse health outcomes, distress screening rates and adequate referrals to psychological support programs among those in need are insufficient in many cancer centers. We therefore aimed to analyze patient- and treatment-related barriers to distress screening and referrals to psychological support as a mandatory component of best-practice cancer care. Method In the present explorative study, latent class analysis was used to identify homogeneous subgroups among 4837 patients diagnosed with cancer between 2011 and 2019. Results Four subgroups were identified. Patients with a mental disorder and psychopharmacology were least probable to be screened for distress. Together with patients aged 65 or older and male patients, they were also less likely to receive psychological support. Patients hospitalized for 28 days or longer were most likely to be both screened and to receive psychological support. Conclusions Clinicians and researchers are recommended not neglect patients with mental disorders and psychopharmacological treatment as well as male and elderly patients when screening for distress and providing access to psychological support.

Few studies have evaluated the influence of valproate on the deterioration of the lipid profile in psychiatric patients. This observational study aimed to compare the evolution of metabolic parameters in a sample of adult patients starting valproate (n = 39) with a control group (n = 39) of patients starting aripiprazole, a drug associated with a low risk of metabolic deterioration. Data were obtained from a prospective study including psychiatric patients with metabolic parameters monitored during the first year of treatment. During the first month of treatment with valproate (median: 31 days [IQR: 25-36]), mean body mass index increased significantly (from 24.8 kg/m 2 at baseline to 25.2 kg/m 2 after one month; P = .03) and mean HDL-C levels decreased significantly (from 1.39 mmol/L to 1.27 mmol/L; P = .02). In comparison, these metabolic variables remained stable during the first month of treatment with aripiprazole. The proportion of patients with early (ie during the first month of treatment) HDL-C decrease of ≥ 5% was significantly higher under valproate (54%) than aripiprazole (15%) treatment (P < .001). These findings remind the importance of a prospective metabolic monitoring in patients who initiate valproate treatment. Further research should be conducted on larger samples and should focus on finding effective interventions to prevent such metabolic adverse effects.

Background The Psychopharmacology Algorithm Project at the Harvard South Shore Program (PAPHSS) published algorithms for bipolar depression in 1999 and 2010. Developments over the past 9 years suggest that another update is needed. Methods The 2010 algorithm and associated references were reevaluated. A literature search was conducted on PubMed for recent studies and review articles to see what changes in the recommendations were justified. Exceptions to the main algorithm for special patient populations, including those with attention-deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), substance use disorders, anxiety disorders, and women of childbearing potential, and those with common medical comorbidities were considered. Results Electroconvulsive therapy (ECT) is still the first-line option for patients in need of urgent treatment. Five medications are recommended for early usage in acute bipolar depression, singly or in combinations when monotherapy fails, the order to be determined by considerations such as side effect vulnerability and patient preference. The five are lamotrigine, lurasidone, lithium, quetiapine, and cariprazine. After trials of these, possible options include antidepressants (bupropion and selective serotonin reuptake inhibitors are preferred) or valproate (very small evidence-base). In bipolar II depression, the support for antidepressants is a little stronger but depression with mixed features and rapid cycling would usually lead to further postponement of antidepressants. Olanzapine+fluoxetine, though Food and Drug Administration (FDA) approved for bipolar depression, is not considered until beyond this point, due to metabolic side effects. The algorithm concludes with a table of other possible treatments that have some evidence. Conclusions This revision incorporates the latest FDA-approved treatments (lurasidone and cariprazine) and important new studies and organizes the evidence systematically.

Aims Public service announcements often create media messages intended to stigmatize negative behaviors to reduce and prevent these behaviors. Drawing on social and cognitive psychology, we hypothesize that stigmatizing messages can create stereotype threat would be associated with shorter latency to first cigarette in the laboratory compared to the control condition. Design A double-blind, randomized, controlled trial in which participants completed two smoking lapse tasks, one at baseline and one post-intervention/control. Setting An experimental psychopharmacology laboratory in the western United States. Participants A community sample of non-treatment-seeking daily smokers (n = 77) received either a stereotype threat (n = 39) or neutral/control (n = 38) message. Intervention Participants received either a stereotype threat message that stigmatized smoking or a control message. Measurements The primary outcome measure was participants' ability to delay smoking during the smoking lapse task in the experimental session FINDINGS: The difference in delay time during the experimental session at the point where 50% of each group had smoked was 3 minutes. Cox proportional hazard models revealed that participants in the stereotype threat group were significantly less able to delay initiating smoking compared to the control group (hazard ratio = 0.504, P = 0.010, 95% confidence interval = 0.30, 0.85), after controlling for baseline latency to smoke. Conclusions Messages that elicit negative stereotypes of smokers operated as 'smoking-promoting messages' in the context of our controlled laboratory investigation.

Objective The endogenous opioid system is assumed to be involved in the pathophysiology of borderline personality disorder (BPD), and opioid antagonists may improve core features of BPD. The aim of this retrospective chart analysis was to evaluate the relative contribution of the opioid antagonist naltrexone and other psychotropic drugs in the improvement of overall symptomatology in BPD. Methods One hundred sixty-one inpatients with BPD treated between January 2010 and October 2013 were classified as either treatment responders or non-responders. Treatment responders were defined as subjects with significant improvements in four or more symptoms from a defined symptom list. The relative contribution of all psychotropic drugs to improvement of BPD symptomatology was assessed by means of a stepwise logistic regression. Results None of the drugs applied contributed significantly to improvement, with the exception of naltrexone (odds ratio [OR] 43.2, p ≤ 0.0001). Patients treated with naltrexone (N = 55, 34%) recovered significantly more often. Higher doses of naltrexone were more effective (OR 791.8, p ≤ 0.0001) than lower doses (OR 26.6, p ≤ 0.0001); however, even low-dose treatment was better than any other pharmacological treatment. Conclusions Naltrexone was associated with improvement in BPD in a dose-dependent manner. The present study provides additional evidence that dysregulation of the endogenous opioid system is implicated in the pathophysiology of BPD symptoms.

Although physicians are aware of the risks of prescribing long-term off-label antipsychotics in people with intellectual disability, attempts to discontinue often fail. This study aimed to identify potential determinants of successful and failed discontinuation. Long-term off-label antipsychotics were tapered in 14 weeks, with 12.5% of baseline dose every 2 weeks. Participants living in facilities offered by intellectual disability service providers, ≥6 years, with an IQ

To facilitate the understanding of pregabalin and optimize its clinical usage in Hong Kong, an expert panel (11 psychiatrists, one family physician and one anesthesiologist) experienced in treating anxiety and somatic symptoms was invited to establish a set of consensus statements based on several discussion areas. A non-systematic literature search for relevant articles was conducted. The panelists addressed the discussion areas by sharing their clinical experience and available literature in a couple of meetings. At the last meeting, consensus statements derived from the proceedings were discussed and finalized. A total of 11 statements were ultimately accepted by panel voting based on their practicability of recommendation in Hong Kong. These statements are aimed to act as a practical reference for local clinicians when they consider prescribing pregabalin in different clinical situations.

Background Pharmacodynamics and pharmacogenetics are being explored in pharmacological treatment response for major depressive disorder (MDD). Interactions between genotype and treatment response may be dose dependent. In this study, we examined whether MDD patients with Met/Met, Met/Val, and Val/Val COMT genotypes differed in their response to bupropion in terms of depression scores. Methods This study utilized a convenience sample of 241 adult outpatients (≥18 years) who met DSM‐5 criteria for MDD and had visits at a Midwest psychopharmacology clinic between February 2016 and January 2017. Exclusion criteria included various comorbid medical, neurological, and psychiatric conditions and current use of benzodiazepines or narcotics. Participants completed genetic testing and the 9 question patient‐rated Patient Health Questionnaire (PHQ‐9) at each clinic visit (M = 3.8 visits, SD = 1.5) and were prescribed bupropion or another antidepressant drug. All participants were adherent to pharmacotherapy treatment recommendations for >2 months following genetic testing. Results Participants were mostly Caucasian (85.9%) outpatients (154 female and 87 male) who were 44.5 years old, on average (SD = 17.9). For Val carriers, high bupropion doses resulted in significantly lower PHQ‐9 scores than no bupropion (t(868) = 5.04, p, Individuals (154 female and 87 male) with major depression disorder (MDD) with Met/Met, Met/Val, and Val/Val COMT genotypes differed in their response to bupropion treatment in terms of PHQ‐9 scores. High‐dose bupropion is beneficial for MDD patients with Met/Val or Val/Val COMT genotypes, but not for patients with Met/Met genotype.

The schism between psychiatry, psychology and analysis, while long present, has widened even more in the past half-century with the advances in psychopharmacology. With the advances in electronic brain imaging, particularly in developmental and post-traumatic stress disorders, there has emerged both an understanding of brain changes resulting from severe, chronic stress and an ability to target brain chemistry in ways that can relieve clinical symptomatology. The use of alpha-1 adrenergic brain receptor antagonists decreases many of the manifestations of PTSD. Additionally, this paper discusses the ways in which dreaming, thinking and the analytic process are facilitated with this concomitant treatment and hypervigilence and hyper-arousal states are signficiantly decreased.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5-HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes. Four online databases (PubMed, Cochrane CENTRAL, PsycINFO, and PharmGKB) were searched for articles on polymorphisms of SLC6A4 including 5-HTTLPR and STin2 by using a systematic approach. Specific and general psychopharmacology terms, along with adverse effect and tolerability concepts, added to the search strategy. The Human Gene Mutation Database was checked for additional references. Forty studies met the inclusion criteria. While null and occasionally opposite associations are reported, the low expression 5-HTTLPR S allele is generally associated with greater adverse drug reaction burden during SSRI therapy. The most convincing evidence is in studies of antidepressant-induced mania and gastrointestinal adverse events. Studies of STin2 are sparse and have conflicting findings. In conclusion, the S allele of 5-HTTLPR may be predictive of increased adverse event burden, and this effect appears specific to certain classes of adverse events. Limitations and challenges in interpreting this body of evidence include assay errors, dissimilar grouping of genotypes, the role of ethnicity in associations, and study methodological differences. The clinical utility of serotonin transporter genotypes is not yet delineated but will ultimately depend on genotypic effects on both tolerability and efficacy of SSRIs.

Prescribing of antipsychotic medications for patients with delirium remains controversial. Concerns exist that these vulnerable and frail patients may be prescribed antipsychotics inappropriately as a substitute for non-pharmacological approaches when identifiable causes are not found or they challenge ward processes. Moreover, recent evidence suggests that antipsychotics may cause more harm than good in the palliative care patient group with delirium. On the other hand, guidelines in the United Kingdom and the Netherlands support prescribing of antipsychotics in certain circumstances, and a large European survey has revealed that antipsychotics tend to be prescribed first line for hyperactive delirium. Never before, therefore, is there a greater need to examine whether indeed these medications are clinically useful for the treatment of delirium. With this in mind, evidence-based arguments for and against prescribing antipsychotics for the treatment of delirium are presented in this debate article. The paper concludes with a moderation piece to help guide clinical practice.

Currently, it has been demonstrated that psychotropic drugs, particularly antidepressants, are frequently prescribed for patients who seek bariatric surgery. Many bariatric surgery patients have a history of a mood disorder. Unlike medications for diabetes, hypertension or hyperlipidemia, which are generally reduced and at times discontinued, postsurgery antidepressants use is only slightly reduced. The Roux-en-Y procedure is most frequently associated with alteration in drug exposure. Medication disintegration, dissolution, absorption, metabolism and excretion have been found to be altered in postbariatric patients, although data are sparse at this time. This paper will review the current evidence regarding the effect of bariatric surgery on drug treatment including mechanism of interference as well as the extent of changes identified to date. Data will be presented as controlled trials followed by case series and reports.

Objective We compared functional impairment outcomes assessed with Sheehan Disability Scale (SDS) after treatment with duloxetine versus selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder. Methods Data were pooled from four randomized studies comparing treatment with duloxetine and SSRIs (three double blind and one open label). Analysis of covariance, with last-observation-carried-forward approach for missing data, explored treatment differences between duloxetine and SSRIs on SDS changes during 8 to 12 weeks of acute treatment for the intent-to-treat population. Logistic regression analysis examined the predictive capacity of baseline patient characteristics for remission in functional impairment (SDS total score ≤ 6 and SDS item scores ≤ 2) at endpoint. Results Included were 2193 patients (duloxetine n = 1029; SSRIs n = 835; placebo n = 329). Treatment with duloxetine and SSRIs resulted in significantly (p

Objective This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. Methods In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions—Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. Results The drug-exposed group (n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group (n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. Conclusions These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings. Copyright © 2015 John Wiley & Sons, Ltd.

Objective The study evaluated relationships between frontal lobe function in patients with schizophrenia and both their social adjustment and medication, using 22-channel near-infrared spectroscopy (NIRS). Methods One hundred ninety-nine stable patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia, whose medication had not been changed within the preceding 3 months and who were able to visit our clinics for NIRS, were the study subjects. As a comparator, 144 healthy volunteers who underwent a physical examination and the Mini-International Neuropsychiatric Interview also received NIRS. Results The main outcomes evaluated were frontal lobe oxyhemoglobin concentration (OxHb) measured by NIRS, current medication, social adjustment, and scores on the Brief Psychiatric Rating Scale. The OxHb in schizophrenic patients (0.878 ± 1.1801 mMmm; n = 199) was significantly lower than that in the healthy volunteers (2.085 ± 1.7480 mM mm: n = 100) (p

The original definition of atypical antipsychotic drugs (APD) was drugs that are effective against positive symptoms in schizophrenia with no or little extrapyramidal symptoms (EPS). However, atypical APD have been reported to be more effective for cognitive dysfunction and negative symptoms in schizophrenia than typical APD, which expands the definition of 'atypicality'. This article provides a critical review of the pharmacology of atypical APD, especially from the viewpoint of receptor binding profiles and neurotransmitter regulations as well as neuroprotection and neurogenesis. A variety of serotonin (5-HT) receptors, such as 5-HT2A / 2C , 5-HT1A , 5-HT6 and 5-HT7 receptors, may contribute to the mechanisms of action of 'atypicality'. The dopaminergic modulations, including a low affinity for dopamine D2 receptors and a partial D2 receptor agonistic action, and glutamatergic regulations may also be involved in the pharmacological backgrounds of 'atypicality'. Atypical APD, but not typical APD, may facilitate cortical neuroprotection and hippocampal neurogenesis, which might be a part of the action mechanisms of atypical APD. The facilitation of cortical neuroprotection and hippocampal neurogenesis induced by atypical APD might be mediated by an increase in the Ser9 phosphorylation of glycogen synthase kinase-3β (GSK-3β). The stimulation of 5-HT1A receptors and/or the blockade of 5-HT2 receptors, which is characteristic of atypical APD, might increase Ser9 phosphorylation of GSK-3β. Moreover, atypical APD increase brain-derived neurotrophic factor (BDNF) levels. BDNF increases Ser9 phosphorylation of GSK-3β and has neuroprotective and neurogenic effects, as in the case of atypical APD. These findings suggest that GSK-3β might play a role in the action mechanisms of atypical APD, in both the 5-HT-dependent and BDNF-dependent mechanisms.

Objective: To describe the pharmacological management of borderline personality disorder (BPD) in Spain from 2001 through 2016, the factors associated with prescriptions, and changes in pharmacotherapy over this time period. Methods: Retrospective, cross-sectional, observational study conducted in a sample of 457 patients with BPD consecutively admitted to a specialist BPD Program between January 2001 and November 2016. Data on sociodemographic and clinical variables, as well as pharmacological treatment upon the admission to the programme, were used to describe pharmacological prescriptions, the factors associated with these medications, and changes in prescription over the last 15 years. Results: Most (88.4%) patients were on pharmacological treatment, with 53.8% of persons taking >= 3 medications. No significant changes in these percentages were observed over the study period. The use of tricyclic antidepressants and benzodiazepines decreased, while the use of atypical antipsychotics increased. Axis I comorbidity was the main factor associated with pharmacological treatment and polypharmacy. Conclusions: This study provides further evidence confirming the worldwide overuse of prescription medications for BPD and shows that there has been a shift in the prescription pattern in the last 15 years. These results suggest that real clinical practice only partially adheres to clinical treatment guidelines.

Objective To provide a neurobiological basis of eating disorders for clinicians and to enlighten how comparing neurobiology and eating disorders with neurobiology of other psychiatric illnesses can improve treatment protocols. Method A selective review on the neurobiology of eating disorders. The article focuses on clinical research on humans with consideration of the anatomical, neural, and molecular basis of eating disorders. Results The neurobiology of people with eating disorders is altered. Many of the neurobiological regions, receptors, and chemical substrates that are affected in other mental illnesses also play an important role in eating disorders. More knowledge about the neurobiological overlap between eating disorders and other psychiatric populations will help when developing treatment protocols not the least regarding that comorbidity is common in patients with EDs. Conclusion Knowledge about the underlying neurobiology of eating disorders will improve treatment intervention and will benefit from comparisons with other mental illnesses and their treatments.

A randomly selected group of Nationally Certified School Psychologists (NCSPs; n = 817) were mailed the 42-item School Psychopharmacology Roles and Training Evaluation (SPRTE) which inquired about their caseloads, practice roles as proposed by DuPaul and Carlson (2005), and prior training in psychopharmacology. A modified Tailored Design Methodology (TDM; Dillman, Smyth, & Christian, 2009), involving four mail-based contacts, was used to yield a 74% survey return rate (n = 607). Of the returned surveys, a 72% (n = 548) usable response rate was obtained and used in the present study. Consistent with prior literature, nearly all (99.6%) school psychologists reported serving at least one student taking psychotropic medication. Primary direct servicerolesincludedmonitoringbehavioralresponsetopsychotropictreatment(28%),monitoring treatment side-effects (23%), and developing psychotropic treatment goals from direct assessment measures (14%). Primary indirect service roles included providing behavior management consultation to teachers of students taking medication (96%), implementing adjunctive psychosocial supports (87%), and providing assessment data to physicians for diagnostic purposes (84%). Despite differencesin established psychopharmacologicaltraining standards, actual practiceroles and training received did not differ between NCSPs from APA-accredited programs and those from National Association ofSchoolPsychologists (NASP)-approvedprograms.Implications forschool psychopharmacology practice, training and research are addressed. C � 2014 Wiley Periodicals, Inc.