Akathisia can sometimes be sufficient reason to change the neuroleptic medication, when lowered dosing or addition of beta-blockers, as described below, are either ineffective or not indicated. In any case, akathisia should never be allowed to fester; this side effect calls for immediate and quick relief.
About one-half of extrapyramidal side effects (EPS) represent akathisia. If akathisia is missed, one-half of the cases of EPS will be misinterpreted as other conditions. Conservative estimates indicate that about 25% of patients treated with traditional neuroleptics develop akathisia. About half of the cases of akathisia are delayed, not occurring until after the first month of treatment, but most cases occur within three months. (There are rare cases of extremely delayed and chronic, or “tardive”, akathisia).
Akathisia has subjective and objective components.
Subjectively, it consists of an intense feeling of dysphoria and extreme anxiety, as occurs with panic attacks.
Objectively, it is associated with observed physical restlessness and an inability to sit still. This restlessness is not necessarily consistent, but it can be intermittent, occurring for a few hours in a day or less. Hence akathisia cannot be ruled out based on lack of observed physical restlessness during an office visit. Clinicians often ask patients whether they feel like they need to “jump out of their skin.” In my experience, if positive, this symptom is almost pathognomonic of akathisia; but its absence does not rule out akathisia.
Based on these characteristics, akathisia is frequently confused with other conditions. In our experience, the most common misdiagnosis is vaguely observed “agitation.” Frequently, such agitation is simply ascribed to the offending medication but this vague description gives no guidance to a clinician about how to manage it. The same issue holds for the more vague term “activation”, which I often hear in relation to atypical neuroleptics as well as SRIs like fluoxetine. Especially with SRIs, many of these cases of “activation” or “agitation” are cases of akathisia. Another common misdiagnosis is mania; this mistake is linked to the “agitation” problem. Sometimes clinicians will observe agitation in a patient with bipolar disorder, and conclude that it represents mania (rather than systematically assessing mania criteria). It is my hunch that many purported cases of “mania” related to atypical neuroleptic use really represent undiagnosed akathisia. Lastly, such agitation can be misinterpreted as worsening psychosis in patients with schizophrenia.
Besides the fact that akathisia represents one-half of cases of EPS, it is important to diagnose this side effect because it is associated with noncompliance and suicidality. We find that many patients can tolerate a mild degree of parkinsonian tremor or rigidity, but even mild akathisia is highly disagreeable, and patients need immediate relief. This usually requires reduction in dosing of the neuroleptic or, where reduced dosing leads to less efficacy, the addition of a beta-blocker like propranolol.
When missed or ignored, akathisia can lead to suicidality. This process sometimes involves a lack of recognition on the part of patients that their intense dysphoria, anxiety, and restlessness may be a side effect; these symptoms are more frequently attributed to their depressive or manic syndromes, leading to demoralization and sometimes suicide is seen as the only viable form of relief. This process may have been related to a number of the cases of fluoxetine-related suicide that have been published. Again, clinicians need to educate their patients about the nature of akathisia, and when it is suspected, all efforts should be made to resolve akathisia as soon as possible so as to reduce the suicide risk.
PL recommends dosing propranolol in its slow-release generic formulation, Propranolol ER, at 60 mg qHS gradually increasing if needed to effect, with a maximum dose of 120 mg qHS. It is important to check a baseline pulse, and to follow the pulse as one increases the dose, not increasing the dose beyond a minimal pulse of 50 beats/minute.
There are no clearly informative studies comparing different kinds of beta-blockers in the treatment of akathisia. Cardioselective agents, such as atenolol, are helpful at times and have the advantage of not crossing the blood-brain barrier, unlike propranolol. Sometimes clinicians will avoid propranolol due to reported risks of depression or sedation related to its CNS activity. Meta-analyses indicate that the relative risk of depression with propranolol is quite low, and in my experience, patients with bipolar disorder rarely appear to develop depressive symptoms in relation to propranolol. Propranolol also has the advantage of providing some direct CNS anxiolytic relief for the subjective experience of akathisia. I therefore tend to begin with propranolol, and only move to cardioselective agents if intolerance to propranolol occurs. Other general risks with beta-blockers can sometimes limit their use, such as the risk of elevation of cholesterol in long-term use, sexual dysfunction (impotence) in men, and a relative contraindication in patients with severe diabetes or asthma.
Here is a classic paper on akathisia.
The data on akathisia with modern dopamine blockers are reviewed here.