Therapeutic Advances in Psychopharmacology

The evidence for the risks associated with anticholinergic agents has grown considerably in the last two decades. Not only are they associated with causing peripheral side effects such as dry mouth, blurred vision and constipation, but they can also cause central effects such as cognitive impairment; and more recently, they have consistently been linked with an increased risk of dementia and death in older people. This paper reviews the evidence for the associations of anticholinergic agents and the risk of dementia and increased mortality in dementia...

Progressive structural brain changes are well documented in schizophrenia and have been linked to both illness progression and the extent of antipsychotic treatment exposure. Literature reporting longitudinal changes in brain structure in individuals with schizophrenia is selectively reviewed to assess the roles of illness, antipsychotic treatment, adherence and other factors in the genesis of these changes. This narrative review considers literature investigating longitudinal changes in brain structure in individuals with schizophrenia...

Delirium is a serious consequence of many acute or worsening chronic medical conditions, a side effect of medications, and a precipitant of worsening functional and cognitive status in older adults. It is a syndrome characterized by fluctuations in cognition and impaired attention that develops over a short period of time in response to an underlying medical condition, a substance (prescribed, over the counter, or recreational), or substance withdrawal and can be multi-factorial. We present a narrative review of the literature on nonpharmacologic and pharmacologic approaches to prevention and treatment of delirium with a focus on older adults as a vulnerable population...

In current medical practice, it is difficult to find any reports claiming that drugs that are primarily anticholinergic or those that have significant anticholinergic effects have any therapeutic benefits. These drugs fell into disrepute within the mental health field from the mid-1960s onwards, and their supposed problems extended to elsewhere in medicine after that. There is considerable evidence that this disrepute stemmed more from marketing copy rather than from hard clinical trial data. Many apparent reviews appear to repeat prior claims rather than present substantial or new evidence...

Aging increases susceptibility both to psychiatric and medical disorders through a variety of processes ranging from biochemical to pharmacologic to societal. Interactions between aging-related brain changes, emotional and psychological symptoms, and social factors contribute to multimorbidity - the presence of two or more chronic conditions in an individual - which requires a more patient-centered, holistic approach than used in traditional single-disease treatment guidelines. Optimal treatment of older adults with psychiatric and medical multimorbidity necessitates an appreciation and understanding of the links between biological, psychological, and social factors - including trauma and racism - that underlie physical and psychiatric multimorbidity in older adults, all of which are the topic of this review...

BACKGROUND: Altered resting-state functional connectivity has been found in patients with post-traumatic stress disorder (PTSD). However, the alteration of resting-state functional connectivity at whole-brain level in typhoon-traumatized individuals with PTSD remains largely unknown. OBJECTIVES: To investigate changes in whole-brain resting-state functional connectivity and brain network topology in typhoon-traumatized subjects with and without PTSD. DESIGN: Cross-sectional study...

BACKGROUND: Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the substance have subsided. These transient effects, sometimes labeled as the 'psychedelic afterglow', have been suggested to be associated with enhanced effectiveness of psychotherapeutic interventions in the subacute period. OBJECTIVES: This systematic review provides an overview of subacute effects of psychedelics...

BACKGROUND: In the last few years, ketamine is becoming increasingly common in the treatment of mental health conditions, but there is a lack of safety data informing intramuscular and sublingual dosing in a community-focused group psychotherapy setting. The Roots To Thrive ketamine-assisted therapy (RTT-KaT) program is a unique 12-week RTT-KaT program with 12 community of practice (a form of group therapy) sessions and three ketamine medicine sessions. OBJECTIVES: This study reports on adverse effects of intramuscular and sublingual ketamine dosing in a community group psychotherapy setting among 128 participants across four cohorts...

BACKGROUND: In patients attempting to discontinue their antidepressant medication, there have been no prospective studies on patterns of withdrawal as a function of the rate of antidepressant reduction during the tapering trajectory, and moderators thereof. OBJECTIVE: To investigate withdrawal as a function of gradual dose reduction. DESIGN: Prospective cohort study. METHODS: The sampling frame consisted of 3956 individuals in the Netherlands who received an antidepressant tapering strip between 19 May 2019 and 22 March 2022 in routine clinical practice...

BACKGROUND: Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always suitable, with a proportion of individuals intolerant of side effects or unable to engage in necessary blood monitoring. Given the profound impact TRS can have on those affected, alternative pharmacological approaches to care are needed. OBJECTIVES: To review the literature on the efficacy and tolerability of high-dose olanzapine (>20 mg daily) in adults with TRS...

Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG. Semaglutide is a weekly injectable GLP-1RA which received recent approval for obesity management and noted superiority over other GLP-1RAs. This study explored the efficacy and tolerability of semaglutide in AAWG among individuals with severe mental illness...

Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine's wide-ranging superior efficacy - for treatment-resistant schizophrenia (TRS) and beyond - and make its safe use eminently feasible...

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022...

BACKGROUND: Anxiety disorders are highly prevalent and chronic disorders with treatment resistance to current pharmacotherapies occurring in approximately one in three patients. It has been postulated that flumazenil (FMZ) is efficacious in the management of anxiety disorders via the removal of α4 β2δ gamma-aminobutyric acid A receptors. OBJECTIVE: To assess the safety and feasibility of continuous low-dose FMZ infusions for the management of generalised anxiety disorder (GAD) and collect preliminary efficacy data...

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Posttraumatic stress disorder (PTSD) is a devastating condition, for which there are few pharmacological agents, often with a delayed onset of action and poor efficacy. Trauma-focused psychotherapies are further limited by few trained providers and low patient engagement. This frequently results in disease chronicity as well as psychiatric and medical comorbidity, with considerable negative impact on quality of life. As such, off-label interventions are commonly used for PTSD, particularly in chronic refractory cases...

BACKGROUND: As an atypical antipsychotic drug, olanzapine is one of the most commonly used drugs for delirium control. There are no systematic evaluations or meta-analyses of the efficacy and safety of olanzapine for delirium control in critically ill adults. OBJECTIVES: In this meta-analysis, we evaluated the efficacy and safety of olanzapine for delirium control in critically ill adults in the intensive care unit (ICU). DATA SOURCES AND METHODS: From inception to October 2022, 12 electronic databases were searched...

BACKGROUND: There is increasing evidence of the association between chronic low-grade inflammation and severe mental illness (SMI). The objective of our study was to assess serum cytokine levels (SCLs) at admission and discharge in a true-to-life-setting population of inpatients with major depression (MD), bipolar disorder (BD), and schizophrenia (Sz), as well as of healthy controls. METHODS: We considered MD, BD, and Sz to be SMIs. We evaluated 206 inpatients [MD, N  = 92; BD, N  = 26; mania (Ma), N  = 44; Sz, N  = 44)...

BACKGROUND: More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited. OBJECTIVES: The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts. DESIGN: Systematic review. DATA SOURCES AND METHODS: PubMed, article references, and Clinicaltrials...

BACKGROUND: Lithium-associated hyperthyroidism is much rarer than lithium-associated hypothyroidism. Yet, it may be of substantial clinical significance for affected individuals. For instance, lithium-associated hyperthyroidism could destabilise mood, mimic manic episodes and impact physical health. Only few studies have explored incidence rates of lithium-associated hyperthyroidism. Even fewer studies have compared incidence rates according to lithium exposure history. OBJECTIVES: To determine the impact of lithium treatment on the incidence rate of hyperthyroidism in patients with bipolar or schizoaffective disorder and assess its aetiology...