Drugs for psychosis and mood that bind dopamine D2 receptors can be classified not only by whether they also block serotonin 2A receptors, but by whether they also bind D3 or D1 receptors.

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA–MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA–MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA–MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.

Musical hallucinations are uncommon phenomena characterized by intrusive and frequently distressful auditory musical percepts without an external source, often associated with hypoacusis, psychiatric illness, focal brain lesion, epilepsy, and intoxication/pharmacology. Their physiological basis is thought to involve diverse mechanisms, including “release” from normal sensory or inhibitory inputs as well as stimulation during seizures, or they can be produced by functional or structural disorders in diverse cortical and subcortical areas. The aim of this review is to further explore their pathophysiology, describing the functional neuroimaging findings regarding musical hallucinations. A literature search of the PubMed electronic database was conducted through to 29 December 2015. Search terms included “musical hallucinations” combined with the names of specific functional neuroimaging techniques. A total of 18 articles, all clinical case reports, providing data on 23 patients, comprised the set we reviewed. Diverse pathological processes and patient populations with musical hallucinations were included in the studies. Converging data from multiple studies suggest that the superior temporal sulcus is the most common site and that activation is the most common mechanism. Further neurobiological research is needed to clarify the pathophysiology of musical hallucinations.

Anxiety disorders are the most prevalent mental disorders and are associated with substantial healthcare costs and a high burden of disease. In this article, changes in the new Diagnostic and Statistical Manual for Mental Disorders (the DSM–5) with respect to panic disorder/agoraphobia, generalized anxiety disorder, social anxiety disorder, specific phobias, and selective mutism are compared with the International Classification of Diseases (ICD–10) system.

Agitation and aggression in adult psychiatric patients with psychoses and in persons with dementia increase the burden of disease and frequently cause hospitalization. The implementation of currently available management strategies and the development of new ones is hindered by inconsistent terminology that confuses agitation with aggression. This confusion is maintained by many rating scales that fail to distinguish between these two syndromes. We review the frequently used rating scales with a particular focus on their ability to separate agitation from aggression. Agitation and aggression are two different syndromes. For example, reactive aggression is often precipitated by rejection of care and may not be associated with agitation per se. We propose, in treatment studies of behavioral symptoms of dementia and challenging behaviors in psychoses, that outcomes should be evaluated separately for agitation and aggression. This is important for investigation of drug effectiveness since the medication may be effective against one syndrome but not the other. Separate assessments of agitation and aggression should be a general principle of trial design with particular salience for registration studies of medications proposed for approval by the U.S. Food and Drug Administration and other regulatory bodies.