THAT LEADS TO GROSS INCOMPETENCE ON THE CLINICAL FRONT,
MANY UNRECOGNIZED INJUSTICES IN THE CRIMINAL SYSTEM, AND
UNTOLD TRAGEDIES– BUT SCIENCE IS PUTTING THE PIECES TOGETHER

Conclusions: Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.

INDEPENDENT FORENSIC SERVICES LLC, 32796 EDWARD DRIVE, CONIFER, CO, 80433, USA

FORENSIC PSYCHIATRIST, PHARMACOGENETICIST, SUITE 310, LEVEL 3 203-223 NEW SOUTH HEAD ROAD, POINT PIPER, NSW, 2027, AUSTRALIA

DEPARTMENT OF BIOLOGICAL SCIENCES, UNIVERSITY OF DENVER, DENVER, CO, 80208, USA

Adverse drug reactions and interactions are among the major causes of death in the United States.

Antidepressants have been reported as causing suicide and homicide and share the class attribute of frequently producing akathisia, a state of severe restlessness associated with thoughts of death and violence.

Medical examiners can now identify some pharmacogenetic interactions that cause drugs, deemed safe for most, to be lethal to others. Such deaths do not yet include medication-induced, akathisia-related suicides and homicides.

An extrapyramidal side effect, akathisia is a manifestation of drug toxicity whose causes lie, inter alia, in drugs, doses, and co-prescribed medications that inhibit andcompete for metabolizing enzymes, which may themselves be defective. In this paper, we report ourinvestigation into adverse drug reactions/interactions in three persons who committed homicide, twoalso intending suicide, while on antidepressants prescribed for stressful life events.

Their histories of medication use, adverse reactions and reasons for changes in medications are presented. DNA samples were screened for variants in the cytochrome P450 gene family; that produce drug metabolizing
enzymes.

All three cases exhibit genotype-based diminished metabolic capability that, in combination with their enzyme inhibiting/competing medications, decreased metabolism further and are the likely cause of these catastrophic events.

Many drugs that cross the blood
brain barrier and a quarter of the medicines in general use are metabolized by the highly poly-morphic cytochrome P450 system.

Blood levels of prescribed medicines can be pushed towards toxicity because of genetically determined metabolizing capacity, high doses, and interactionswith co-prescribed CYP450 inhibitors and synergies.

Genetics of the cytochrome P450 (CYP450) system are the otherwise invisiblefactor that can correlate with catastrophic behavioural distur-bances.

A forensic investigation combined with medication history, reports from observers, clinical records and a blood sample or a non-invasive swab from the living or dead can help elucidate the proximate, pharmacogenetic cause of death, suicide or violence.

This determination can absolve persons charged with homicide (or abort the investigation), affect insurance pay-outs for suicide, provide an absolute defence of involuntary intoxication for the
perpetrator of violence, and should protect a living person from getting more drugs with the same metabolic pathways as those that caused the problem.

​”Well, we DO have a handle on one specific problem and that is the
brand new boxed
dosage warning for poor or rapid metabolizers, who make up 8% of Caucasians [3-8% of Black/African Americans] for whom dosage must be adjusted up to 75% – and by that I mean DOWN.

So, if you do not heed the boxed warning, and prescribe a normal dose (and we all know what happens if you complain from there; the dose is adjusted UP) then serious adverse effects will occur, including suicidality and homocidality.

And, there is a TEST for this condition, so I say a great first step is to INSIST on the test before prescribing. No real doctor would pass this by.

​Let’s see what happens.

https://www.accessdata.fda.gov/…/021436s038,021713s030…​

See 2.7 on p.7 ​of Abilify Prescribing Information:

Dosage Adjustments for Cytochrome P450 Considerations

Dose Adjustments for ABILIFY in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducer
From the US Food & Drug Administration (FDA) — Abilify’s 84-page Prescribing Information, including the “Black Box” warning — see p. 47 >>>>>>

8.6 CYP2D6 Poor Metabolizers Dosage adjustment is recommended in known CYP2D6 poor metabolizers due to high aripiprazole [Brand names — Abilify, Abilify Maintena, and Aristada] concentrations.

Approximately 8% of Caucasians and 3–8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see DOSAGE AND ADMINISTRATION (2.7) and CLINICAL PHARMACOLOGY (12.3)].

Colorado’s Visionary Mental Health Advocate Amy Smith

FDA PRESCRIBING INFO ON ABILIFY