Psychosis due to neurologic conditions

Abstract

Psychosis arises with considerable frequency in a number of neurologic conditions. The treatment of such patients is often challenging, as many of the treatments for psychosis pose some risk of worsening the underlying neurologic condition. Although psychosis may emerge in the context of any neurologic condition that sufficiently disrupts the functioning of or connections between limbic, paralimbic, frontal, subcortical areas mediating complex sensory perception, interpretation, and thought or language organization, secondary psychoses are most often encountered in patients with Alzheimer's disease (Parkinson's disease receives dopaminomimetic therapies) and epilepsy. Psychosis, and particularly delusions and visual hallucinations, may arise in Alzheimer's disease. Based on the available literature, the first-line therapy for this problem is risperidone 0.5 to 3 mg per day. If this treatment proves unsuccessful, low-dose haloperidol or olanzapine should be considered next. If these treatments prove unsuccessful, quetiapine should then be considered. Finally, clozapine may be useful for treatment-refractory psychosis due to Alzheimer's disease, but due caution is warranted given its considerable anticholinergic properties and potential for worsening cognition in these patients. Although disease-emergent psychosis (paranoid delusions and visual hallucinations) may develop in patients with Parkinson's disease, psychosis due to dopaminomimetic therapy is much more common. When such symptoms develop, the accepted first step is to taper anti-parkinsonian medications were possible. Anticholinergic medications, amantadine, selegiline, and dopamine receptor agonists should be reduced or discontinued, provided that the patient can tolerate changes in motor symptoms attendant to such reductions. When these reductions are not feasible or fail to improve treatment-emergent psychosis, low-dose quetiapine or clozapine may be useful. The greatest body of evidence supports the effectiveness of these treatments and their relative lack of adverse effects on motor function. When psychosis develops in the context of epilepsy, the generally accepted first step is to maximize anticonvulsant therapy in an effort to reduce the possible contribution of electrophysiologic disturbances in the described areas to psychotic symptoms. When interictal psychosis persists despite such adjustments, initiation with low-dose atypical antipsychotics carries the least risk of lowering seizure threshold and should be considered.

5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice

“…Atypical antipsychotic drugs (APDs) are the first choice for treating schizophrenia (SZ) and they act primarily through blockade or partial antagonism of dopamine (DA) D 2 receptors and inverse agonism at serotonin 2A (5-HT 2A ) receptors, together with activities at other DA and 5-HT receptors (Meltzer et al, 1989;Roth et al, 2004). Psychotic disorders include SZ, schizoaffective disorder, bipolar disorder, major depression, and various neurological conditions (Arciniegas et al, 2001;Wigman et al, 2012;Landqvist-Waldö et al, 2015). The limited efficacy of atypical APDs for treating negative symptoms and cognitive impairment in SZ, and the role of N-methyl-D-aspartate receptor (NMDAR) antagonists to induce cognitive deficiency in man and laboratory animals implicates glutamate (Glu) and γ-aminobutyric acid (GABA) receptors in some aspects of SZ (López-Gil et al, 2010).…”

Delusions in frontotemporal lobar degeneration

“…Aside from their implications for clinical diagnosis, delusions in FTLD are of considerable neurobiological interest due to the potential insights they hold into the brain mechanisms that link information about external reality with internal representations of the world. Such mechanisms are likely to involve neural networks in the frontal and temporal lobes that are particularly vulnerable in FTLD [13].…”

Olanzapine‐Associated Diabetes Mellitus

“…1 In addition to approved indications, it has been administered for the treatment of a variety of other conditions including psychosis in dementia and Parkinson' s disease, delusional or resistant depression, conduct disorders, aggression, agitation, resistant anxiety disorders, and delirium. [3][4][5][6] Known adverse reactions to olanzapine include orthostatic hypotension, weight gain, akathisia, increased salivation, and somnolence. 1 Published reports of hyperglycemia occurring in association with olanzapine began occurring in 1998.…”