Clinical Psychopharmacology

An Introduction and My Vision for JCP No abstract available

In Memoriam: Frederick King Goodwin (1936–2020) No abstract available

James (Jeff) Walter Jefferson, MD No abstract available

Comparison of the Metabolic Characteristics of Newer Second Generation Antipsychotics: Brexpiprazole, Lurasidone, Asenapine, Cariprazine, and Iloperidone With Olanzapine as a Comparator Purpose/Background Extensive research has been conducted comparing the metabolic characteristics of older second-generation antipsychotics (SGAs); minimal data exist comparing the long-term metabolic effects of SGAs approved in the last 10 years. Methods/Procedures A retrospective chart review of patients treated with brexpiprazole, lurasidone, asenapine, cariprazine, and iloperidone (newer SGAs) for at least 6 weeks at an outpatient psychiatric practice was conducted. Patients treated with olanzapine, an older SGA, were included as a comparator. Metabolic characteristics were collected at baseline, approximately 6 weeks, 12 weeks, and for up to 12 months. Findings/Results Of the newer SGAs, there were statistically significant increases in patients' average weight at 12 weeks and 1 year or less with brexpiprazole (2.48 lb, P = 0.02; 5.97 lb, P = 0.01) and iloperidone (4.54 lb, P < 0.01; 5.13 lb, P = 0.02). Brexpiprazole and iloperidone resulted in significant increases in body mass index, up to a 0.90-kg/m2 average increase in patients taking brexpiprazole at 1 year or less. Minimal weight gain was seen with cariprazine (4.25 lb, P = 0.42) and asenapine (1.80 lb, P = 0.62) at 1 year or less after treatment initiation. Although not statistically significant, lurasidone showed an average weight loss of up to 0.60 lb at 1 year or less (P = 0.56). Implications/Conclusions Although some weight gain was seen with the newer SGAs, all demonstrated significantly favorable metabolic characteristics compared with olanzapine. Monitoring of weight and metabolic parameters remain important in patients treated with SGAs.

Guideline Adherence of Monitoring Antipsychotic Use for Nonpsychotic Indications in Children and Adolescents: A Patient Record Review Background Antipsychotics are frequently prescribed to children and adolescents for nonpsychotic indications. Guidelines recommend regularly assessing treatment response and adverse effects and the ongoing need for their use. We aimed to assess adherence to recommendations of available guidelines regarding monitoring antipsychotic use and to test the influence of children's age, sex, intelligence quotient, and diagnosis on adherence. Methods We reviewed 426 medical records from 26 centers within 3 large Dutch child and adolescent psychiatry organizations, excluding children with schizophrenia, psychosis, mania, or an intelligence quotient below 70. We investigated whether there was regular assessment of treatment response, adverse events (physical and laboratory), and at least annual discussion of the need of continued use. Results On average, treatment response was assessed in 69.3% of the recommended treatment periods, height in 25.6%, weight in 30.6%, blood pressure in 20.6%, evaluation of adverse events in 19.4%, and cardiometabolic measures in 13.7%; discontinuation and/or continued need was discussed at least annually in 36.2%. Extrapyramidal and prolactin-related adverse effects, waist circumference, glucose, and lipids were rarely investigated. Higher age was associated with lower rates of assessment of treatment response. Most antipsychotics were prescribed long-term. In those children with sufficient documentation of the course of treatment, 57.7% was still using an antipsychotic 3 years after initiation. Conclusions Our findings indicate insufficient adherence to guideline recommendations for monitoring antipsychotic use in children and adolescents, as well as long duration of use in the majority of children. Especially, older children are at higher risk of receiving suboptimal care.

Clozapine Response in Schizophrenia and Hematological Changes Background Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. Methods Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as "much," or "very much" improved on the seven-point Clinical Global Impression—Improvement (CGI-I) subscale. Results In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. Implications Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

Nanocurcumin as an Add-on to Antipsychotic Drugs for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study Purpose/Background It is well documented that one of the pathophysiological mechanisms of negative symptoms in patients with schizophrenia is hypofunction of N-methyl-d-aspartate receptors. This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of nanocurcumin as an adjuvant agent on psychotic symptoms, especially negative symptoms, in patients with chronic schizophrenia. Methods/Procedures Fifty-six inpatients with stable chronic schizophrenia and predominant negative symptoms were randomized in a 1:1 ratio to nanocurcumin soft gel capsule (160 mg/d) and control groups, along with their antipsychotic regimen for 16 weeks. The efficacy of treatment was assessed by Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Clinical Global Impressions—Severity, and Clinical Global Impressions—Improvement scales. Extrapyramidal symptoms were evaluated by Simpson-Angus Scale and Barnes Akathisia Rating Scale. Patients were assessed at baseline and weeks 4, 8, 12, and 16 after the medication started. Findings/Results No significant differences were observed in demographic or clinical variables between both groups at baseline. The nanocurcumin group showed significantly greater improvement on the negative subscale (P = 0.05), the general psychopathology subscale (P < 0.001), the positive subscale (P = 0.004), total Positive and Negative Syndrome Scale (P < 0.001), Clinical Global Impressions—Severity (P < 0.001), and Clinical Global Impressions—Improvement scores (P < 0.001) in comparison with the control group at the endpoint. Extrapyramidal symptom rating scales and Calgary Depression Scale for Schizophrenia and frequency of other adverse effects were comparable between 2 groups. Implications/Conclusions The present study indicates nanocurcumin as a safe and potential adjunctive treatment strategy for treatment of primary negative symptoms of schizophrenia.

Prolactin and Estrogen Levels in Postmenopausal Women Receiving Aripiprazole Augmentation Treatment for Depression Background Antipsychotic drugs are well established to alter serum prolactin levels, often resulting in adverse effects including amenorrhea, galactorrhea, osteoporosis, and loss of libido. There is growing preclinical evidence that prolactin-elevating drugs can instigate the progression of precancerous lesions to breast cancer and that genes activated by prolactin are associated with the development and proliferation of breast cancer. Current guides advise a cautious approach (weighing risks and benefits) to the administration of prolactin-elevating antipsychotic drugs in women with a previously detected breast cancer. Aripiprazole is known to be a prolactin-sparing antipsychotic; however, data regarding its effects on prolactin and estrogens in postmenopausal women are lacking. Methods We examined serum hormone levels in n = 66 women who participated in a randomized, double-blind, placebo-controlled, multicenter trial of aripiprazole (high and low doses) added to an antidepressant in adults older than 60 years. Aripiprazole or placebo tablets were administered for 12 weeks as an augmentation strategy in venlafaxine-treated women. The primary outcomes were the difference in prolactin and estrogen levels. Results There was no significant effect of aripiprazole treatment on prolactin or estrogen levels, including in models that divided groups into low and high doses: prolactin (P = 0.075), estrone (P = 0.67), and estradiol (P = 0.96). Conclusions Aripiprazole addition to an antidepressant did not alter serum estrogens or prolactin. These findings may be relevant in the treatment of some postmenopausal women with depression.

Cost of the Illness of Treatment-Resistant Schizophrenia: A Mirror Image Study Comparing Clozapine With Other Antipsychotics Purpose/Background This study aimed to evaluate and compare the cost of illness in patients with treatment-resistant schizophrenia (TRS) during 3 months before starting clozapine and for the initial 3 months of treatment with clozapine. Methods/Procedures Fifty-two patients with TRS were evaluated for the cost of illness (direct, indirect, and provider cost) by using a structured questionnaire for the period of 3 months before starting clozapine and then at the end of the 3 months of clozapine therapy. Findings/Results Total treatment cost for the period of 3 months before starting clozapine was Indian rupees (INR) 40,372 (560.72 US dollars), and the total treatment cost for the first 3 months of clozapine therapy was INR 40,553 (563.23 US dollars). At both the assessments, indirect cost formed the main bulk of the total cost, with no significant difference in the indirect cost. The total direct treatment cost reduced from INR 13,931.6 (193.49 US dollars) to INR 8756 (121.61 US dollars), and the difference between the 2 assessments was statistically significant, with an advantage for clozapine. Overall, after starting clozapine, the total direct cost reduced from 34.5% to 21.6%, and the total indirect cost reduced from 54.3% to 40.2%. After starting clozapine, total provider cost increased from 11.2% to 38.2% of the totalcost. Implications/Conclusions Treatment with clozapine is not associated with a significant increase in the overall treatment cost, in the short term. However, there is a significant reduction in direct treatment costs.

The Effect of Add-on Buprenorphine to Matrix Program in Reduction of Craving and Relapse Among People With Methamphetamine Use Disorder: A Randomized Controlled Trial Background Methamphetamine addiction is a global issue. Buprenorphine might have beneficial roles in reducing craving to methamphetamine use via altering neurotransmission signaling and dopaminergic system-related reward mechanisms. Procedures This clinical trial was performed in 2019 to 2020 in Khorshid Hospital, Isfahan, Iran. The study was conducted on patients with methamphetamine use disorder. The intervention group received sublingual buprenorphine for 8 weeks, and the other group also received placebo tablets. Patients were followed up and visited every month for the next 4 months. Both groups were treated simultaneously by matrix program for 2 months and observed for the next 4 months. Patients filled out the Cocaine Craving Questionnaire-Brief (CCQ-Brief) every week during intervention time (first 2 months) and every month during follow up visits (4 months). The Depression Anxiety Stress Scale (DASS-21) was also filled out before and after interventions for all of the patients. Data were analyzed using SPSS software using χ2, independent t test and repeated-measure analysis of variance tests. Results Our data indicated significantly lower CCQ-Brief scores in the intervention group compared with the placebo group (P < 0.05). It was also indicated that changes in CCQ-Brief scores were also significant among both groups (P < 0.001). We also showed that the anxiety, depression, and stress scores reduced significantly after interventions (P < 0.001). These scores were also significantly lower in the intervention group compared with placebo group (P < 0.05). Conclusions Buprenorphine may be effective and may have positive potential roles in reducing methamphetamine craving. This drug is also helpful in reducing the anxiety, depression, and stress of patients with methamphetamine use disorders.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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