Psychopharmacology bulletin最新文献

Introduction: This article will demonstrate that the most widely used versions of the Hamilton Rating Scale for Depression (HAM-D) used in randomized clinical trials, the Guy 1976 HAM-D¹ and the SIGH-D,² have response options that deviate sharply from Max Hamilton's 1960³ and 1967⁴ guidelines. For example, difficulty in concentration, one of the diagnostic criteria for a Major Depressive Episode according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) since 1980, in editions III, IV, IV-TR and 5,⁵ is something that Hamilton wrote should be measured in his scale, yet it is not measured in either of the presently used HAM-Ds.

Method: A review was conducted of the four key papers related to the development of the Hamilton Rating Scale for Depression: the 1960 and 1967 papers by Max Hamilton; the HAM-D chapter in the 1976 ECDEU Assessment Manual for Psychopharmacology edited by William Guy; and the 1988 article on the Structured Interview Guide for the HAM-D (SIGH-D) by Janet Williams. Additionally, the Janet Williams updated 2013 SIGH-D⁶ is also reviewed.

Results: When comparing the HAM-D and the SIGH-D with the gold standard Hamilton guidelines from his 1960 and 1967 articles, 13 of the 17 items contain significant errors.

Conclusion: Significant differences between the currently used HAM-Ds and the guidelines set forth by Max Hamilton in 1960 and 1967 will be demonstrated. These discrepancies may produce inconsistencies in administration and scoring, leading to unreliable measurements of subjects' and patients' depressive symptoms and unreliable measurement of their progress over time.

Bipolar Disorder (BD) is a mental disorder characterized by periods of depression and abnormally elevated moods. Recent studies proposed the existence of a correlation between inflammation, disease severity and response to antipsychotic therapy. The present study is aimed to investigate if treatment with second-generation antipsychotic, in monotherapy, influences the inflammatory process in BD patients. In 50 hospitalized BD patients who started monotherapy with second-generation antipsychotic, we investigated, after six-week of treatment, both clinical outcomes and change in inflammatory markers such as C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR). We observed a significant improvement of clinical symptoms (measured through MADRAS, YMRS, CGI and BPRS scales) in all treated patients. Moreover, we found that at the time of enrolment BD patients showed higher CRP levels compared to reference value, and that after 6 weeks of antipsychotic treatment CRP (but not ERS) plasma levels were significantly reduced returning to reference levels. The present exploratory study indicates that monotherapy with antipsychotic drugs reduces, not only BD symptoms, but also an inflammatory marker such as PCR. The evaluation of relationship between antipsychotic treatment and patients inflammatory conditions could be usefulness in clinical practice, both providing a marker to drug response, and permitting the identification of new targets in BD therapy.

Inadequate response to antidepressant treatment, in a significant proportion of patients diagnosed with Major Depressive Disorder, contributes to the large burden of disability associated with the disease; thus, predicting treatment response is one of the most important challenge for clinicians who deal with depressed patients. The cytokine hypothesis of depression suggests that altered pheripheral cytokine levels are involved in the pathophysiology of depressive disorder and in modulating response to treatment. Present meta-analysis aimed to investigate the association between cytokine levels at baseline and response to antidepressant therapies. Authors performed a systematic search of PubMed and Embase databases for studies published between 2010 and January 2021: of 3345 identified records, 31 studies met the inclusion criteria for the qualitative synthesis, whereas 19 studies were eligible for quantitative analysis. Patients who failed to respond to antidepressant had aberrant inflammatory process, namely higher baseline levels of C-Reactive Protein and Interleukine-8, which is associated with treatment outcome in Major Depressive Disorder. Despite these promising results, further investigations are needed in order to replicate the data and to examine the potential role of inflammatory marker as a novel predictive tool for pharmacological treatment of depressive disorder.

Stuttering, a disturbance in the normal fluency and time patterning of speech is usually developmental. In some cases, it is acquired, and causes include stroke, brain tumor, and trauma. Implicated in the causation of stuttering are overactive presynaptic dopamine systems in the region of the brain that modulate verbalization. It is a rare side effect of antipsychotic medications and has been reported with phenothiazines, clozapine, and risperidone. This is a report of a patient who developed stuttering when treated first with chlorpromazine and later with risperidone. Patient had a diagnosis of schizoaffective disorder and had been treated with antipsychotic medications including haloperidol, olanzapine, and paliperidone. He developed stuttering for the first time upon receiving intramuscular injections of chlorpromazine for treatment of agitation. The stutter improved and eventually resolved. He subsequently presented with a severe stutter when he was treated with risperidone. The stutter improved after risperidone was discontinued. It is speculated that drug-induced stuttering may be a manifestation of akathisia leading to noradrenergic and serotonergic mechanisms being implicated. It could be that either the cholinergic, dopaminergic or serotonergic systems are involved or that there is an imbalance of these systems that may be relevant.

We present the case of a young gentleman with diagnoses of bipolar affective disorder, high body mass index, and obstructive sleep apnoea. He was commenced on zuclopenthixol due to an inadequate response to quetiapine, but this swiftly led to marked physical health deterioration including shortness of breath, back pain, tachycardia, tachypnoea, and hypoxia. He was urgently transferred to hospital where he required intubation and intensive care admission. AFTER excluding other causes, it was felt that commencing zuclopenthixol had induced laryngo-pharyngeal dystonia leading to upper airway compromise and severely impaired respiratory function. He progressively recovered after zuclopenthixol was stopped, and he was transferred back to the psychiatric hospital after eight days. THIS case highlights the potential challenges in diagnosing this rare but potentially fatal reaction to antipsychotics. We review the available literature on other cases including a potential interaction between typical antipsychotics and serotonin-specific reuptake inhibitors. Psychiatrists and emergency physicians should be aware of this condition and be alert in considering the administration of anticholinergics, which could be a simple yet life-saving intervention.

Avoidant/Restrictive Food Intake Disorder and misophonia seem to be overrepresented in autism spectrum disorder. Literature is mute on psychopharmacotherapy in these complex presentations. Here, authors report on a challenging case of low-functioning ASD child with comorbid ARFID and misophonia that responded favorably to a low-dose risperidone. This is followed by a brief discussion of purported pharmacodynamic mechanisms and relevant literature.

Purpose: To determine if enhanced flow cytometry (CellPrint™) can identify intracellular proteins of lithium responsiveness in monocytes and CD4⁺ lymphocytes from patients with bipolar disorder.

Methods: Eligible bipolar I or II patients were openly treated with lithium for 16-weeks. Baseline levels of Bcl2, BDNF, calmodulin, Fyn, phospho-Fyn/phospho-Yes, GSK3β, phospho-GSK3αβ, HMGB1, iNOS, IRS2, mTor, NLPR3, PGM1, PKA C-α, PPAR-γ, phospho-RelA, and TPH1 in monocytes and CD4⁺ lymphocytes of lithium responders and non-responders were measured with CellPrint™. Their utility of discriminating responders from non-responders was explored. Protein-protein network and pathway enrichment analyses were conducted.

Results: Of the 24 intent-to-treat patients, 12 patients completed the 16-week study. Eleven of 13 responders and 8 of 11 non-responders were available for this analysis. The levels of the majority of analytes in lithium responders were lower than non-responders in both cell types, but only the level of GSK3β in monocytes was significantly different (p = 0.034). The combination of GSK3β and phospho-GSK3αβ levels in monocytes correctly classified 11/11 responders and 5/8 non-responders. Combination of GSK3β, phospho-RelA, TPH1 and PGM1 correctly classified 10/11 responders and 6/7 non-responders, both with a likelihood of ≥ 85%. Prolactin, leptin, BDNF, neurotrophin, and epidermal growth factor/epidermal growth factor receptor signaling pathways are involved in the lithium treatment response. GSK3β and RelA genes are involved in 4 of 5 these pathways.

Conclusion: CellPrint™ flow cytometry was able to detect differences in multiple proteins in monocytes and CD4⁺ lymphocytes between lithium responders and non-responders. A large study is warranted to confirm or refute these findings.

Purpose of review: Insomnia affects more than 10% of the population and causes significant discomfort and disability. Suvorexant is an orexin receptor antagonist that specifically targets the wake-sleep cycle. This review summarizes recent and seminal evidence in the biological and physiological evidence of insomnia, the mechanism of action of suvorexant in treating insomnia, and clinical evidence regarding its use.

Recent findings: There is no single clear diagnosis for insomnia, and thus prevalence is not entirely clear, but it is estimated to affect 10%-30% of the adult population. Comorbidities include obesity, diabetes, and various psychiatric conditions, and insomnia likely has a contributing role in these conditions. Insomnia, by definition, impacts sleep quality and also wakefulness, including academic success and work efficiency. Insomnia is likely related to genetic susceptibility and a triggering event, leading to hyper-arousal states and functional brain disturbances. This leads to hyperactivity of the hypothalamic-pituitary-adrenal axis, over-secretion of corticotropin-releasing factor, and aberrancy in neurotransmitter release. Though several pharmacological options exist for the treatment of insomnia, there is equivocal data regarding their efficacy or limits to their use due to side effects and contraindications. Suvorexant is a novel dual orexin receptor antagonist, which is shown to improve sleep by reducing arousals. Unlike classical therapeutics, suvorexant does not alter the sleep profile; it prolongs the time spent in each sleep state. Though it may cause some somnolence, it is milder than reported with other drugs.

Summary: Multiple clinical studies support the use of suvorexant in insomnia. In primary insomnia, suvorexant is effective (over placebo), as measured by polysomnography and reported by patients, in both attaining and maintaining sleep. Similar, albeit to a smaller degree, results were found in secondary insomnia. Suvorexant carries two significant advantages over existing therapies; it has a much better safety profile in approved doses, and it preserves natural sleep architecture, thus promoting more restful sleep and recovery. Unfortunately, data exists mostly for suvorexant versus placebo, and head-to-head trials with common hypnotics are needed to assess the true efficacy of suvorexant over the alternatives. And while tolerance is less likely to develop, close monitoring of post-marketing data is required to evaluate for long term adverse events and efficacy.