Antidepressants and Violence: Problems at the Interface of Medicine and Law
Driven To Drink: Antidepressants and Cravings for Alcohol I became verbally aggressive and my behavior was reckless. On one . It makes sense that if some people have a genetic link to alcoholism mediated through the. Alcohol also causes a loss of inhibition and increases aggressive behaviour Because alcohol can damage the liver, the levels of these antidepressants in the body What causes the link between alcohol and depression?. What a new study on antidepressants and youth violence does and A possible link, however, between this class of selective serotonin.
Pertinent clinical trial data have been generated but remain unavailable. Combining datasets might make it possible to establish whether the risks of treatment are related to age and gender, or whether those with and without prior histories of aggression are affected similarly. While it may be that further data would show that the risk associated with certain SSRIs and tricyclic antidepressants may be less than others, or may not exist in all antidepressants, there is no way to make that determination without access to these data.
Indeed, the issue of violence triggered by older antidepressants has been raised before [ 38 ]. Current warnings in the US and Canada are consistent across antidepressants, but in other countries, for instance in the UK see Summaries of Product Characteristics on the Electronic Medicines Compendium Web site, http: Given the new medico-legal issues some of these cases pose, it may well fall to the courts to demand that data now unavailable be made public.
Conclusion The new issues highlighted by these cases need urgent examination jointly by jurists and psychiatrists in all countries where antidepressants are widely used. The problem is international, and it would make sense to organise an international effort now. In practice, clinicians need to be aware of the issues, but serious violence on antidepressants is likely to be very rare. When violence is a suspected outcome, every case has to be considered carefully, on the principle that individuals are responsible for their conduct, unless there is clear evidence of compromised function that cannot be otherwise explained.
These did not involve suicidality, aggressive behaviour, or other serious disturbance. All prior episodes had resolved within several weeks. In DS had had an episode of depression, which his doctor treated with fluoxetine. He had a clear adverse reaction to fluoxetine involving agitation, restlessness and possible hallucinations, which worsened over a three-week period despite treatment with trazodone and propranolol that might have been expected to minimise the severity of such a reaction.
After fluoxetine was discontinued DS responded rapidly to imipramine. Ina new family doctor, unaware of this adverse reaction to fluoxetine, prescribed paroxetine 20 mg to DS, for what was diagnosed as an anxiety disorder. Two days later having had, it is believed, two doses of medication, DS using a gun put three bullets each through the heads of his wife, his daughter who was visiting, and his nine-month-old granddaughter before killing himself. SmithKline Beecham was deemed 80 percent responsible for the ensuing events [ 1 ].
The documentary evidence included an unpublished company study of incidents of serious aggression in 80 patients, 25 of which involved homicide. Experts for the plaintiff suggested that the mechanism through which paroxetine contributed to these events was probably akathisia or psychosis.
A central problem with both akathisia and psychosis in such contexts is that the takers of medications often fail to recognise the fact that the state they are in is drug-induced and that discontinuing treatment can alleviate the symptoms.
Alcohol, Drugs and Aggression | Dual Diagnosis
Within days, she became markedly somnolent, agitated, and emotionally labile. There was an increasing series of arguments at home, and unprecedented aggression. After eight weeks, her parents, concerned about the situation, brought her back to the GP, who increased the dose of paroxetine to 30 mg.
One week after the increase of dose and two months after the initial prescription, NH was involved in an incident at a nightclub in which she assaulted another person. The dose of paroxetine was reduced to 20 mg.
Her behaviour remained unstable, disinhibited, and there was at least one suicidal act. Three months later she stopped treatment. She had significant withdrawal problems, but her behaviour normalised.
Having been out of work for close to a year she went back to work and has remained in employment since. NH pled not guilty by virtue of an automatism. This case appears to have involved treatment-induced akathisia. He had no history of violence or suicidality, and had remained gainfully employed throughout.
During one of these episodes, DH was given sertraline Zoloft by a GP and clearly responded adversely to this, most notably with agitation.
- Drinking alcohol during antidepressant treatment — a cause for concern?
- Antidepressants and Violence: Problems at the Interface of Medicine and Law
He stopped treatment the following day on medical advice. In Julyhe sought help from his GP, who was on leave. DH was seen by a locum who admitted in Court that he had not checked DH's file before prescribing sertraline 50 mg. That night, apparently feeling worse after a first dose of sertraline, DH took four more doses of sertraline.
The next morning, after his wife got up he met her in the kitchen and strangled her. He then set off in his car, having decided to kill himself, but turned round and contacted the police to tell them what had happened. He decided he should accept the consequences of his actions and did not want to distress his family further.
DH's lawyers had intended to defend the case on the basis of non-insane automatism or involuntary intoxication, but before the proceedings in Maythe Crown made an offer that if DH pleaded guilty to manslaughter on the basis of substantial impairment, the Crown Prosecutor would not contest any defence submission that DH be released from gaol on the date of his sentence.
Further, the Crown accepted the case put forward by the defence implicating sertraline. DH accepted that offer in view of his age The judge in his summing-up released DH and stated: This case might best be explained in terms of a treatment-induced akathisia or delirious state. Case 4 MB was a year-old woman with two children who had untreated nervous problems since her teenage years. In she approached her GP who prescribed paroxetine.
An initial 20 mg dose was increased to 30 mg. MB appeared to become more anxious and agitated. During these increases, the medical notes record her as being more anxious and agitated, but did not link this to treatment. She made plans to take her own and her children's lives, and taking the children for a drive, attached a hosepipe to the exhaust. In the course of two efforts to execute this plan, she thought better of it and informed both the police and child-care authorities what had happened.
Her children were taken into care and she was charged with attempted murder. During the sentencing in the Supreme Court of Western Australia in Aprilthe judge stated there were substantial grounds for implicating venlafaxine in MB's behaviour, and gave her a suspended sentence [ 41 ]. This case again appears to involve treatment-induced akathisia. Case 5 AT had a baby daughter in December at the age of She has not planned to as she would not do that to her daughter and has no immediate plans of suicide of any description.
Two days later she stole another phone. Four days later, a psychiatrist noted: Three weeks later she attempted robbery with an offensive weapon. In October, a forensic psychiatrist examining her in prison noted that for the preceding two months, while in prison she had been prescribed mirtazapine 30 mg nightly a non-SSRIand had become calmer and better able to discuss her situation. Her first two offences took place 17 and 19 days after she started fluoxetine. They appear to have been impulsive and were marked by complete lack of feeling.
The third, fourth, and fifth offences occurred after a dose increase. The fifth offence involved brutal violence and use of a flick knife.
The prison assessment took place when she had been off the drug for about ten weeks, long enough to eliminate the drug. Her final charges involved robbery and assault as well as child neglect. Based on the medical records, one of us AH noted in his report to the court that AT appeared to have suffered treatment-induced emotional blunting. However, the judge in this English case doubted that the effects of the drug could explain the deliberate planning of robberies and she was found guilty and sentenced to three years in prison with no allowance for any contribution from fluoxetine.
An appeal was rejected. Case 6 MC started drinking alcohol socially in at the age of He used ecstasy in but stopped after a bad experience. After July MC's cocaine use reduced to nil, apart from four minor relapses. He had none after May MC's alcohol use increased to four to five cans of lager a night in When he missed a tablet of paroxetine, he wanted to hide under a duvet and to stay away from everybody; his hands shook, and he had headaches and nausea.
These symptoms lasted a couple of days, and he learned not to miss a dose. He was also started on a regular zopiclone prescription at this point to counter paroxetine stimulation. Soon after, another doctor in the practice changed him to the more sedating dothiepin, but after a few weeks he asked to be put back on paroxetine.
He subsequently stopped cocaine but began drinking more heavily. Prescriptions of paroxetine and zopiclone continued through to July At this stage he was estranged from an ex-partner with whom he had a now month-old daughter. In Augustat her home, after ten pints of lager, he took two zopiclone tablets. Following an argument, they had a pint of beer each, during which there was another bout of quarrelling, and she went to bed alone, leaving him to sleep on the sofa.
MC may have taken four more zopiclone tablets. He appeared later that night blood-stained in the local police station with his daughter in his arms. The police found his partner dead from multiple stab wounds. He was charged with murder. In prison paroxetine 30 mg was continued; zopiclone was stopped. Intense frightening nightmares have been reported regularly in healthy volunteers taking paroxetine. MC had no reported episodes of sleepwalking before using paroxetine, but he had a number of documented episodes of sleepwalking after starting the drug, and two first-degree relatives had a history of sleepwalking.
Sleepwalking has been reported in association with zolpidem, a hypnotic related to zopiclone [ 42 — 44 ], but no case of sleepwalking on zopiclone has been reported in the scientific literature. However, as noted above, zopiclone is the drug most commonly linked to sleepwalking in Yellow Card reports to the MHRA.
Clearly violence follows domestic arguments, and is a known effect of alcohol, but this case offers grounds also to implicate paroxetine and zopiclone. Zopiclone is known to cause a dose-dependent confusion and amnesia comparable to that found with benzodiazepines [ 45 ].
Violence cannot however be attributed to a direct effect of paroxetine alone, since MC had been maintained on this for almost one year with no prior violence. In these circumstances MC pleaded guilty at his trial on 27 February The judge did not accept that paroxetine and zopiclone had played any part, and sentenced him to 13 years prison.
An appeal against the sentence is being prepared. Case 7 JB was 66 years old, married to a second wife ten years his junior. They had marital difficulties, with frequent arguments but no history of violence.
JB had medical complaints and longstanding depression and anxiety. Digestive symptoms were treated with an antispasmodic combined with chlordiazepoxide 5 mg four times daily ; generalised anxiety was also treated with chlordiazepoxide 10 mg twice daily ; an undiagnosed movement disorder, characterized by twitches and tics, was treated with clonazepam 0.
In addition, JB had been treated with the antidepressant doxepin 75 mg at night for years. Concerned about the sedative effects of his medication, JB's wife began replacing active doxepin powder with sugar in an attempt to offset this effect. JB suspected the capsules had been tampered with.
His wife admitted doing this when they saw a new psychiatrist in mid-August The doctor considered JB to have major depression with anxiety, complicated by physical symptoms and marital strife. He noted that JB was not psychotic or suicidal, and agreed that doxepin be discontinued, instead prescribing fluoxetine 10 mg daily, continuing the other medications as before.
JB was meticulous about compliance and even kept a medicines log. He remained concerned that his wife was tampering with his pills, and after four weeks fluoxetine accused her of being unfaithful.
Alarmed at his suspicions, his wife rang the psychiatrist and disposed of the household gun. Meanwhile, JB's friends noted that, normally placid, he had become tense, strange, and suspicious; he asked for a replacement gun to defend himself; described a plan to escape an expected attempt on his life; feared poisoning of food and drink; feared an ambush when visiting his mother's grave. Two months after starting fluoxetine JB had become floridly deluded, expecting to be attacked or poisoned by his wife, or her agent.
The psychiatrist received phone calls of concern from friends and family but did not alter his treatment. One evening in mid October JB approached his neighbours, covered in blood, reporting an attack by his wife.
He had several minor cuts to his arms. His wife was found dead in their hallway, in a pool of blood with stab wounds. Ina Mississippi court found JB not guilty of murder by reason of insanity [ 46 ]. He was confined to a mental hospital, where he remains, even though on review of his medical notes by one of us DMit was clear that his psychosis cleared on withdrawal of fluoxetine, and further treatment. His physicians are concerned about the risk should he be discharged.
Although prescription drugs were not invoked in his defence, a subsequent civil case seeking damages from Eli Lilly Prozac and Hoffman LaRoche benzodiazepines was settled in personal communication from plaintiff's lawyer, R. This homicide case involves a treatment-induced psychosis. Case 8 LD, a year-old mother, separated from the father of her 3-year-old twin boys in After a protracted custody battle, she began experiencing episodes of dizziness, sweating, shaking, nausea, and pressure in the chest.
She was well between episodes, experienced no suicidality, irritability, or aggression, and continued to care for her sons as before, living in the same house as her father and his second wife. She contacted her family doctor, but no appointments were available and she saw the nurse practitioner instead.
She was given a free starter pack of sertraline 25 mg, and a prescription for alprazolam 0. Other unexpected effects were that her previous moderate alcohol intake took on a compulsive quality, and she became increasingly depressed and began to think of suicide. Alarmed, she tried to see her doctor, but he was not available. LD's agitation, restlessness, depression, and suicidal ideas worsened.
Two days after the switch to paroxetine, she claims she took double the prescribed amount of both paroxetine and alprazolam, hoping this would help. She drank alcohol and sounded intoxicated on the phone. Claiming she saw no future for herself or her children, she shot both in the head just before their afternoon nap. She recalls intending to kill herself as well, but did not do this immediately as she noticed one son was still breathing.
Her blood and urine alcohol levels showed marked intoxication. The Florida State Attorneys initially sought to have LD convicted of murder and sentenced to death, but later dropped pursuit of the death penalty. The defence team contended that LD was not guilty by reason of temporary insanity caused by the prescription drugs provided by the nurse practitioner.
The judge ruled that evidence could be admitted indicating that akathisia was associated with SSRI treatment, but that a causal relationship could not be argued. With this restriction on defence testimony, the State Attorneys convinced the jury that the drugs did not play a causal role in the homicides.
LD was convicted, and sentenced to life without possibility of release [ 47 ].
Despite the difficulties of his social situation, he had no record of treatment for nervous disorders or of violence or behavioural disturbance. Following an argument with his father at the end of Octoberhe was admitted to a behavioural centre for six days where he was started on paroxetine. His behaviour worsened daily on paroxetine. He was discharged against medical advice to the care of his grandparents, who, when his paroxetine ran out, took him to their primary-care physician who prescribed sertraline 50 mg, increasing this to mg two days before the killings for which CP was charged.
The duration of sertraline treatment was three weeks. After the prescription of sertraline, CP was involved in a number of aggressive incidents at school, the first on record for him, and was reported by family members and church members to be restless and talking unusually volubly. Relatives noted a series of risky behaviours.
On the day of the killings, his grandparents had told him that he could not take the school bus following an episode of aggression toward one of the other children on the bus. Later that evening he attended choir practice with his grandparents, who in response to escalating difficulties had warned him he might have to be returned to his father. No company sent a specific case report; most referred only to the number of cases in the Medicines and Healthcare products Regulatory Agency Yellow Card register.
Alcohol, Drugs and Aggression
One claimed that the text of the reports was confidential. None of the international companies referred to cases reported outside the UK. To drink or not to drink? Almost all discouraged alcohol use and, in something of a mixed message, cited evidence from healthy volunteer studies that their drug did not appear to interact with alcohol. The warnings to avoid alcohol are thus unsupported by specific evidence.
They appear weak and unconvincing for both prescribers and patients. This may explain why many patients do not take the warning seriously. We have described a syndrome of pathological intoxication, often with serious consequences, in patients prescribed an SSRI or related drug.
That may relate both to the well known under-reporting of adverse events, and the possibility that regulators have not routinely considered such effects by drug class. The reports are aggregated by individual drug name and relationships between drugs are not visible. This should improve prescribing choices and facilitate detection and study of the problem.
References 1 Allen D, Lader M. Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects. International Clinical Psychopharmacology ;4 Suppl 1: Study on performance and alcohol interaction with the antidepressant fluoxetine.
Substance use disorder comorbidity in major depressive disorder: Efficacy of fluvoxamine in preventing relapse in alcohol dependence: Drug and Alcohol Dependence ; Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: Journal of Psychopharmacology ; International Journal of Risk and Safety in Medicine ; British diplomat cleared of drunk flying charges: Provocation by alcohol of violence as a side-effect of antidepressants.