Acetylcholinesterase inhibitors in treatment-resistant psychotic depression

Abstract

Case reportMr M, a 53-year-old White man, had a 25-year history of recurrent, refractory psychotic depression (World Health Organization ICD-10 revision F33.3) that necessitated over 30 hospital admissions. Identifiable triggers were lacking and remission rarely achieved. Excepting childhood anxiety, he was well adjusted before first presentation. Drug or Alcohol misuse did not feature. Treatments of adequate dose and duration included: antidepressants from every major class, alone and in combination; lithium and carbamazepine augmentation; antipsychotics (first and second generation, oral and parenteral) including clozapine, which was stopped due to neutropenia; numerous electroconvulsive therapy (ECT) courses, approximating 600 stimulus deliveries; psychosurgery twice (bilateral anterior capsulotomy in 1996 and anterior cingulotomy in 1999), both producing unsustained responses. Postsurgical absence seizures responded to lamotrigine, but his depression did not. He remained out of hospital periodically with the support of his family and a combination of regular medication, as required chlorpromazine and maintenance ECT.In July 2012, he was admitted electively during maintenance ECT (135 bilateral stimulus deliveries) whilst taking nortriptyline (300 mg daily), amisulpride (300 mg daily), chlorpromazine (300 mg daily) and lamotrigine (100 mg daily). ECT caused marked cognitive impairment but when stopped, in November 2012, his psychotic depression worsened. He described -with horror -seeing and hearing a "foul-smelling dark man" and could not understand why others did not. This multimodal hallucination was mood congruent, and involved threats to kill the patient's family unless he committed suicide. He often mistook the ward for his home, required physical contact to ensure that staff were 'real' and had vivid dreams of being burned or drowned.Rivastigmine was prescribed (4.2 mg/day transdermal patch) off-licence in January 2013. His hallucinations lessened and resolved fully within a month; his mood improved concurrently. Drugs with anticholinergic properties were withdrawn during this period. Regrettably, intolerable side effects emerged: sialorrhoea, uncontrolled by hyoscine or ipratropium bromide 0.03% spray, resulted in aspiration pneumonia. Donepezil Acetylcholinesterase inhibitors in treatment-resistant psychotic depression Chris Smart, Hamish McAllister-Williams and David Andrew CousinsAbstract: Dopamine receptor antagonists can be effective in psychotic depression but response is not assured. Visual hallucinations may arise from a dysregulation of brain cholinergic systems and acetylcholinesterase inhibitors (AChEIs) can treat such hallucinations in dementia with Lewy bodies (DLB). AChEIs have been used in schizophrenia with some success but their efficacy and tolerability in psychotic depression is unclear. This striking case illustrates AChEIs specifically targeting multimodal hallucinations in treatment-resistant depression. To our knowledge it is the first case report to do so. It highlights the val...

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The Pharmacology of Visual Hallucinations in Synucleinopathies

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Repurposing Cholinesterase Inhibitors as Antidepressants? Dose and Stress-Sensitivity May Be Critical to Opening Possibilities

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