Subject 8, a mother (26-year-old-female; genotypes: CYP2D6 *2/*4, CYP2C9 *1/*1, CYP2C19 *2/*17), was initially prescribed paroxetine for stress. On paroxetine, she experienced an uncharacteristic episode of rage and attempted suicide by inhalation of carbon monoxide from a car exhaust, so she stopped taking it. Two years later, she was prescribed paroxetine again and reassured about its safety. The second time she experienced intense restlessness, surges of rage and anger, marital troubles, panic attacks, impulsive spending sprees, and constant suicidal ideation. She reasoned that her low self-esteem, insomnia, and suicidal behavior were due to difficulties with her in-laws. She overdosed and was admitted to hospital where paroxetine was increased. She tried to kill herself again and was diagnosed with an "adjustment disorder," a stress-induced state. She was switched to venlafaxine, 37.5 mg/day and it was increased to 300 mg/day over 3 months. Each upward dose adjustment occasioned a week spent in bed with exhaustion, as she was unable to get up (akinesia). Her mental state deteriorated and violent outbursts and suicidal ideation became frequent and severe. Unable to stay in one place, she drove several hundred miles with her children and tried to kill them and herself by car exhaust. A few days later she tried to kill her children and herself again. There were no interacting drugs in her regimen, however, her genotype for 2D6 (*2/*4) places her in the intermediate metabolizer category, for which there is evidence of at least twofold increases in serum-venlafaxine levels in both single dose and steady-state studies. Moreover, case reports have documented serious venlafaxine-related adverse events, which are either suspected or confirmed to have resulted from above-therapeutic-range serum-venlafaxine levels; the events ranged from psychosis to hallucination, psychomotor agitation, and delirium.
The subject pleaded diminished responsibility to four charges of attempted murder and was not required to complete time in prison. She recovered fully on withdrawal.
Wyeth has provided the following information in product information for venlafaxine, Effexor  XR, including homicidal ideation, since 2005. (Note: frequent is 1/10; infrequent, 1/100; rare, 1/1000; suicide attempts and homicidal thinking are catastrophic effects, irrespective of frequency.)
Body as a whole - Frequent: chest pain substernal, chills, fever, neck pain; Infrequent: face edema, intentional injury, malaise, moniliasis, neck rigidity, pelvic pain, photosensitivity reaction, suicide attempt, withdrawal syndrome; Rare: appendicitis, bacteremia, carcinoma, cellulitis.
Nervous system - Frequent: amnesia, confusion, depersonalization, hypesthesia, thinking abnormal, trismus, vertigo; Infrequent: akathisia, apathy, ataxia, circumoral paresthesia, CNS stimulation, emotional lability, euphoria, hallucinations, hostility, hyperesthesia, hyperkinesia, hypotonia, incoordination, manic reaction, myoclonus, neuralgia, neuropathy, psychosis, seizure, abnormal speech, stupor, suicidal ideation; Rare: abnormal/changed behavior, adjustment disorder, akinesia, alcohol abuse, aphasia, bradykinesia, buccoglossal syndrome, cerebrovascular accident, feeling drunk, loss of consciousness, delusions, dementia, dystonia, energy increased, facial paralysis, abnormal gait, Guillain-Barre Syndrome, homicidal ideation, hyperchlorhydria, hypokinesia, hysteria, impulse control difficulties, libido increased, motion sickness, neuritis, nystagmus, paranoid reaction, paresis, psychotic depression, reflexes decreased, reflexes increased, torticollis.
Common: Abnormal dreams, decreased libido, dizziness, dry mouth, increased muscle tonus, insomnia, nervousness, paraesthesia, sedation, tremor. Uncommon: Apathy, hallucinations, myoclonus. Rare: Convulsion, manic reaction, neuroleptic malignant syndrome (NMS), serotonergic syndrome.
Very little of the above-quoted information appears in Australian product information for Efexor . It contains no black box warning, denies differences in metabolism between poor and extensive metabolizers, and lists only for nervous system: