Handbook of Drug Interactions

6. Antipsychotic Drugs and Interactions 191
The delay in onset of akathisia suggests that traditional antipsychotics’ causative
influence is indirect—namely, the antipsychotics initiate a chain reaction that, for some,
culminates in akathisia.
Further shrouding the neurochemical understanding of akathisia is its treatment;
beta-blockers and benzodiazepines, which improve akathisia, act in a general manner
on both the central and peripheral nervous system (22). Therefore, unlike the anticholinergics,
for example, the mystery of why akathisia can be improved by broadly acting
drugs conceals the neurochemical and neuroanatomic mechanisms responsible for akathisia
in the first place.
Fluphenazine and haloperidol are especially relevant to consideration of akathisia
and other high-potency side effects such as tardive dyskinesia. These two antipsychotics
are often prescribed in oil-based depot forms that are injected into fatty areas of the
buttocks or rear shoulder, and release themselves steadily into the bloodstream over a
period of 2–4 wk (23).
Since the onset of akathisia is more common weeks after a medicine has begun,
and since those patients on depot medicines have the prospect of slowly metabolizing
antipsychotics accumulating in their system, these patients are at higher risk for developing
akathisia. Because patients taking depot haloperidol or fluphenazine are managed
as outpatients, their akathisia may go undetected, relative to the discomfort of
someone on a hospital ward who is under intermittent observation all day, every day.
An additional dilemma associated with akathisia is that patients often find it difficult
to express the source of their discomfort or restlessness. Families or physicians
may note a sense of increasing distress, and may mistakenly—and sometimes understandably—attribute
that disquiet to psychosis, from undertreatment or noncompliance
with the antipsychotic. If the psychiatrist’s reaction is to then increase the dose of the
dopamine-blocking antipsychotic, the akathisia only gets worse. By the time the basis
for the patient’s discomfort is identified, the mounting discomfort may cause the patient
to refuse further treatment—or worse.
2.3. Civil and Criminal Law and Implications of Akathisia
Those who experience akathisia feel a driven pressure to keep moving, and the
effects are enough to have been occasionally associated with suicide (24).
The clinician must distinguish akathisia’s internal discomfort from the outward
expression of discomfort, through hostility and assaultiveness. Theoretically, one might
imagine a scenario in which someone is so uncomfortable from his akathisia that he
might strike out at another. However, resolving this idea requires factoring in a person’s
inherent predisposition to assaulting others to begin with.
The notion of someone’s violence arising exclusively from akathisia in a person
who is not otherwise violent is unsubstantiated in the clinical literature. As such, this
notion would likely not achieve Daubert standards for having been systematically studied
and confirmed as a cause–effect relationship between akathisia and violence.
2.4. Tardive Dyskinesia
Tardive dyskinesia baffled clinicians for decades. This involuntary and disfiguring
twisting movement of muscles of the face, tongue, hands, or feet (25) was found
in people who had been treated with traditional antipsychotics, particularly those who