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It is obvious, if not platitudinous, that men and women who are abnormally aggressive and impulsive are especially likely to get into trouble with the law, and many of them will end up behind bars. Some of them will obey prison rules and regulations and stay out of any more trouble, at least until they are released from the “joint.” Others will prove to suffer from schizophrenia, intellectual disabilities or traumatic brain injury and – judging from prevailing standards in present-day, punitive America – will languish untreated in their cells until they have served their time. That leaves a substantial proportion of psychiatrically challenged inmates with aggressive impulses that make them dangerous to other inmates, to prison guards, to themselves and to society (once they are released).

Thanks to the psychotropic drug revolution, inmates of our “correctional” institutions are being corrected with a plethora of drugs – antidepressants, antipsychotics, anxiolytics, anticonvulsants, mood stabilizers, and other powerful mind-altering pharmaceuticals.

It is not the purpose of this article to deride the use of psychoactive drugs with prison inmates when there exists a psychiatrically or medically proper indication that such use will benefit the inmates or prevent harm to others. No one would deny that forensic psychopharmacology is a civilized alternative to the truncheon or the hole. Nevertheless, there is an important caveat, and that is the qualifier “proper.

Proper forensic psychopharmacology does not begin with a marginally trained prison employee popping a pill into an inmate’s mouth, although that is the rule rather than the exception in many if not most jurisdictions. American penology has largely given up on rehabilitation and cure in favor of retribution. That measure should be reserved for the very end of the process, except in situations where inmates become violently aggressive. Rather, the beginning of the process is – admittedly ideally in this world of budget-cutting – a thorough medical and psychiatric workup to identify conditions such as brain tumors, seizures, chronic schizophrenia and other disorders that might account for the main reason that prisoners are medicated: aggression. All too many prisoners with treatable illnesses languish untreated year after year because the state department of corrections did not budget for the most fundamental standard of humane care: a thorough workup.

Fortunately, solid case law has addressed the thorniest legal and ethical issues involved in medicating persons whose freedom is already circumscribed, i.e. the issue of informed consent and the right to say “no.” The Supreme Court set the “constitutional minimum” in the case of Washington v. Harper. This case gave much deference (as usual) to corrections administrators based on the governmental interest in keeping prisons “safe” – and there was discussion about how prison is inherently a dangerous place, and would be more so if it was made too difficult to medicate inmates who are acutely psychotic. The court held that due process was satisfied by conducting an intra-institutional hearing with a lawyer, psychiatrist and psychologist to make the decision.

States are able to enact more, but not less, stringent standards than the Supreme Court developed. One example of this is New York. The controlling case is Rivers v. Katz, which gives inmates the right to a full due process adversarial hearing if their psychiatrist wants to medicate over their objection. This can be a real protection: for example, in New York inmates get a Mental Hygiene Legal Services (MHLS) attorney who vigorously cross-examines the doctor, as, frequently, do the presiding judges. One author has been quite surprised over the seriousness with which the courts take medication over objection. In most Supreme Court of the State of New York cases dealing with the subject, the court does not use friendly language when considering antipsychotic medication.

These long-term, non-acute forms of involuntary medication must be distinguished from “emergency medications” – which can be given without legal oversight if the inmate suddenly becomes an acute danger to himself or others as a result of mental illness.

Consequently, once other causes have been ruled out, forensic psychopharmacology devolves around the management of aggression.

Acute aggression is a psychiatric emergency. One of us (JLK,IV) identifies two strategies. The first relies on antipsychotics, either the older first-generation (Haldol) drugs or the newer second-generation agents (Zyprexa, Geodon). The second alternates Haldol with Ativan, an anti-anxiety medication. The strategies work like this:

Haldol is administered in a dose of 5 to 10 milligrams and the patient is reassessed closely for the need for further dosing.

The second strategy alternates 5 mg of, typically, Haldol IM every 30 minutes with 1-2 mg of Ativan, also every 30 minutes, until the prisoner is calm. In some situations, the medication Benadryl is added, both for its sedating property, as well as its ability to counteract any untoward muscle stiffness resulting from the rapid dosing of Haldol.

The various drugs for managing acute aggression differ not only in potency (Haldol is roughly 100 times more potent than Thorazine) but also in their pharmacological “profiles.” For example, Thorazine can cause side effects such as dry mouth or even temporary urinary retention; such side effects are much rarer with Haldol, but the downside is that Haldol causes a much higher incidence of neuromuscular side effects, among them akathisia, a state of muscular and mental restlessness. Among the second generation antipsychotics, Geodon can be toxic to the heart; specifically, it prolongs the QTc interval, a period on the electrocardiogram that corresponds to the repolarization or “recharging” of the lower two chambers of the heart, namely the ventricles; rarely, it causes a sometimes-fatal condition called ventricular fibrillation, or extremely rapid beating of the lower chambers of the heart, leading to a loss of cardiac pumping ability. Persons at risk for this condition can be identified before Geodon is ever given by means of a routine EKG – but, tragically, such EKGs are rarely if ever administered during an aggressive episode that calls for the drug. Zyprexa is a heavily sedating antipsychotic; its steepest downside is that long-term use can cause diabetes – which is not a consideration in taming the fury of acute aggression.

What about Ativan? It is not an antipsychotic, but it has powerful calming properties – most of the time. Benzodiazepines (including Ativan) are widely used in human and veterinary medicine to control aggression. Rarely, Ativan or other benzodiazepines can cause an opposite effect – a paradoxical reaction [Veterinary Psychopharmacology; Crowell-Davis SL, Murray T; 2006 chapter 2] Paradoxical reactions have also been reported in humans. On the plus side, combining Ativan with Haldol attenuates the discomfort of akathisia, not only because the dose of Haldol is lower but because benzodiazepines are widely used for treating akathisia.

Treating Chronic Aggression

Antidepressants

Depression, not surprisingly, is probably the most common mental disorder in prisons. Depression is closely linked to aggression. The symptoms of depression-related chronic aggression are irritability, impulsiveness (“acting out”), and of course a grim, often resentful mood. Not surprisingly, the Selective Serotonin Reuptake Inhibitors, generally prescribed for depression, are probably the most widely used drugs for treating aggression, but we note that these drugs – Prozac, Zoloft, Paxil and others, known collectively as SSRIs – take anywhere from two to six weeks to kick in, so they are definitely not suitable for managing acute aggression. A second caveat is that the inmate must suffer from impulsivity in order to benefit from an SSRI. SSRIs are generally well-tolerated, with fewer bodily side effects than most of the older tricyclic antidepressants (TCAs). Human beings are not the only species whose aggression is ameliorated by both TCAs and SSRIs (See Veterinary Psychopharmacology, ibid).

Anticonvulsants

This broad family of drugs – Dilantin, Valproic Acid,Tegretol Trileptil, Depakote – are indicated for episodic rage attacks, problems with impulse control, head injury and other conditions. One of the most interesting drugs in forensic psychiatry is Trileptil. It is related to Tegretol but, according to an interview with Jeffrey A. Mattes, MD, of the Psychopharmacology Research Association of Princeton, NJ, who has been studying the use of Trileptil in a New Jersey prison, it is better tolerated than other anticonvulsants, and therefore makes the inmate’s life more satisfactory.

Anticonvulsants are thought to work on two related areas of the brain: the evolutionarily ancient limbic system, which includes the amygdala, a structure that has been linked to rage; and the temporal lobes, situated at the sides of the head, which are implicated in today’s neurology as the site of “partial complex seizures” (PCS).

All anticonvulsants have some side effects. VPA and Depakote are rough on the stomach; Dilantin can cause excessive hair growth; Tegretol, and to a lesser extent Trileptil, can cause central nervous system side effects such as hallucinations.

Lithium

As far back as 1976, Michael Sheard, a Yale biologist, took an interest in the use of lithium to control impulsive aggression. In a classic experiment, he gave lithium to 20 violent prison inmates, and placebos to another 20. The placebos had no effect. Interestingly, lithium had no effect on minor infractions like lying and stealing, but it induced a dramatic decrement in attacks on guards and other inmates. Then the 40 prisoners were “crossed over”: When the 20 prisoners theretofore on lithium were switched to placebos, their violent, impulsive aggression returned.

Today, lithium is a fundamental drug in forensic psychopharmacology. Importantly, its uses have been sharpened. Experience shows that lithium is particularly effective for impulsivity, aggression associated with a negative mood, and violence associated with mental retardation. Since lithium is also a fundamental drug for treating bipolar (manic-depressive) disorder, it might be wondered whether “violent” prisoners are actually bipolar. This is false. The reason is that violent prisoners require notably lower doses of lithium than bipolar prisoners. This raises the intriguing question of whether lithium exerts an impulse-controlling effect, independent of its anti-bipolar efficacy. We suspect that the answer will turn out to be “yes.”

In the doses used to control impulsive aggression, lithium is well-tolerated. It is an American practice to measure lithium blood levels a couple of times a year, but the ritual has been abandoned in Europe, where it is recognized that patients will show clinical signs of toxicity before the blood measurement ever comes back from the laboratory. Clinical signs like confusion and tremor are more quickly recognized indications of toxicity than blood levels.

Antipsychotics

The old (Thorazine, Haldol, Stelazine) and the new (Zyprexa, Risperdal, others) antipsychotics should probably be reserved for managing acute aggression, as discussed above, and for treating violent psychotic patients, usually schizophrenics. At least theoretically, they ought to also be useful in prisoners with “borderline” personality disorders, namely, conditions that do not meet “hard” diagnostic criteria for schizophrenia, such as auditory hallucinations. However, antipsychotics – both old and new – have many side effects, so we think they should be reserved for schizophrenia and severe borderline states that do not respond to psychotherapy – assuming any kind of psychotherapy is available to the inmate!

One particular antipsychotic – actually an old drug that was taken off the market for some years because of a cornucopia of side effects, notably a sometimes-fatal plunge in white blood count called agranulocytosis, and then restored to market with Draconian warnings – deserves mention. It is Clozaril, which is remarkably effective for treating schizophrenia that is associated with aggression and suicidality when other antipsychotics fail to produce a therapeutic response. This drug must be especially carefully monitored, but it does produce measurable therapeutic benefits, and so should not be cast out of the pharmacological armamentarium.

Beta Blockers

The paradigmatic beta blocker – a class of drugs that blocks the action of adrenaline and noradrenaline, lowering the heart rate – is Inderal. Others that have been used to treat aggression are Pindolol and Nadolol. Silver and Yudofsky, in a review and rigorous clinical trial (J Neuropsychiat Clin Neurosciences 1999;11:328) reported that between 1977 and the publication of their article, 30 papers had appeared on the efficacy of beta blockers in treating aggression. In the ensuing 14 years, more papers have come out, and the indications for beta blocker therapy for aggression have been sharpened. Beta blockers are appropriate drugs for aggressive schizophrenics, as well as those whose aggression is linked to akathisia (a good reason for minimizing the prescribing of antipsychotics) or head injury. This is not to suggest that beta blockers treat the core symptoms of schizophrenia, although back in the ’70s some British psychiatrists claimed success in treating schizophrenia with Inderal (Yorkston NJ et al Br Med J 14 December 1974; 4:633). Unfortunately, the theory never went anywhere because many patients received antipsychotics along with megadoses of Inderal. We think Peet is probably correct (Br J Psychiat 1981 Aug:139:112) in his report that Inderal simply increased the bioavailability of antipsychotics. Nevertheless, we wonder why we couldn’t find any papers on the use of Inderal as an add-on to minimize the doses of the much more toxic antipsychotics.

The authors of this article both have considerable experience with beta blockers for psychiatric indications. These drugs – originally developed for treating high blood pressure and cardiac arrhythmias – are quite benign in their side-effects profile. This makes them especially attractive for treating aggression – whether or not they will ultimately prove to have an antischizophrenic effect in their own right. In this context, it is worth drawing attention again to the paper by Silver and Yudofsky, who note that some 300 aggressive patients had been tried on antipsychotics, anxiolytics, anticonvulsants and lithium before being successfully treated with beta blockers (ibid). A typical dose of Inderal is 20 mg four times daily – about the same range used in cardiology.

Neurotransmitters

Psychopharmacology is not an orderly science. The major discoveries in psychopharmacology were made in a backwards way, often with years of labor in between. The drugs came first, and only later scientists sought to figure out how they work.

The classical example is Thorazine, which is now known to block the receptor for dopamine (the “dopaminergic” theory of schizophrenia). Dopamine is the primary neurotransmitter released by amphetamines and is linked to irritability and aggression. But in personal communications to the first author, as well as his extensive writings, H.M. Van Praag postulated that a second neurotransmitter, serotonin, also played a role in schizophrenia, mediating visual hallucinations and aggression.

It would be very convenient if we could match up a particular neurotransmitter with a particular form of aggression. We seem to have had the best luck with serotonin, where the SSRIs seem to have a specific anti-aggressive effect in humans and animals. But how does serotonin work? It has been implicated not only in schizophrenia, but also in depression, panic disorder, free-floating anxiety, the premenstrual syndrome, obsessive-compulsive disorder, and other conditions. In fact SSRIs are used to treat a number of these conditions. So where is one to begin to unravel the knot?

The third classical neurotransmitter in the brain is noradrenaline, and it may be the blockade of this neurotransmitter that accounts for the anti-aggressive effects of beta blockers.

Modern molecular biological techniques have hastened drug development by enabling us to isolate the receptors for various neurotransmitters, so there is hope that we may enhance our understanding of the neurobiology of aggression. In the meantime, all across the country, psychotherapists are out in the cold.

Many states have slashed their budgets for individual psychotherapy in prison; the best that most inmates can hope for is some group therapy led by a psychiatric technician, not even a trained psychologist. To appreciate how bad the situation can be, a former colleague of one of the authors hired for a short locum tenens stint in an Arizona correctional facility found only three drugs – Elavil, Haldol, and Valium – when he inspected the pharmacy cabinet in the prison hospital. That’s it: three old drugs with which he was expected to treat the cornucopia of mental illnesses that confront a prison psychiatrist. He quit.

To be sure, psychopharmacology has exerted a major impact on the treatment of violent, impulsive prisoners. But any good psychiatrist will tell you that drugs and psychotherapy work best when they work hand in hand. The politicians who dole out money to our “correctional” system have not gotten the message.