Treatment Emergent Violence To Self And Others; A Literature Review of Neuropsychiatric Adverse Reactions For Antidepressant And Neuroleptic Psychiatric Drugs And General Medications

Abstract

Objective: This paper reviews the literature linking physical violence, directed towards self or others, to serotonergic and dopaminergic psychiatric drugs and general medications.

Design/methodology/approach: Data about side effects, pharmacogenetics and homeostasis are obtained from articles, electronic Medicines Compendium, DSM-IV-TR, British National Formulary (BNF) and academic books. Statistics have been obtained from articles, The National Confidential Inquiry into Suicide and Homicide by People with Mental Illness, Centre for Mental Health and Risk, Manchester, Mental Health Equalities, National Mental Health Development Unit and the NHS Health and Social Care Information Centre. Classification for neurotoxic conditions and mental illness are obtained from the DSM-IV-TR, DSM-V and ICD-10.

Findings: Psychiatric drugs and some general medications have effects that are not always the ones intended. Reactions to different drugs and drug-drug combinations are governed by individual metabolising rates. Phase 1 metabolism takes place via the cytochrome P450 enzymes with 57 human genes identified that are genetically variable i.e. polymorphic. The population are coded as poor, extensive (known as normal), intermediate or ultra rapid metabolisers. Variations in the serotonin transporter gene (5-HTTLPR) and serotonin receptors (5-HT) influence the outcome of serotonergic medications. It is established genetic polymorphisms in the CYP450 and serotoninergic metabolising system cause higher drug blood levels which are associated with neuropsychiatric adverse drug reactions (ADRs), such as akathisia. If not recognised, akathisia, which often precedes violence, suicidality, homicide, mania and psychosis, may be mistaken for new or emergent mental illness and treated with further ineffective, counter-productive psychiatric drugs.

Research limitations/implications: The absence of pharmaceutical data for CYP450 diminishing, null/non- functioning or multiple polymorphisms and variations in the 5-HTTLPR and 5-HT, linking general medications and psychiatric drugs with neuropsychiatric behavioural reactions is notable. There is limited information linking psychiatric drug disruption of homeostasis and neurotransmitters with violence. These issues indicate a need for greater pharmaceutical transparency and further research into the role of CYP450, 5-HTTLPR and 5-HT polymorphism associated neuropsychiatric ADRs for all psychiatric drugs and serotonergic general medications.

Practical implications: Safer prescribing is important and could be achieved by individual genotype testing, which would identify persons with genetic polymorphisms, who are unable to metabolise drugs. Prevention of violence would enhance peoples' well being, ground floor practitioner and public safety.

Conclusion: This paper is the first review that implicates certain drugs as a cause of violence due to pharmacogentic polymorphisms and neurotransmitter disruption.