Dear Editor:
The case report by Dr. Padder on the onset of akathisia leading to suicidal ideation associated with low dose aripiprazole treatment [Psychiatry 2006 2006;3(4):40–3] is an important case analysis of not just the properties of aripiprazole but the usage of antipsychotics in patients who abuse illicit drugs. The patient mentioned in the case report had a history of phencyclidine (PCP) abuse, and that could have contributed to the increased sensitivity to develop extrapyramidal side effects (EPS) and akathisia.
Patients with a history of substance abuse have an increased risk of developing EPS. Even though this patient may not have been actively abusing PCP at the time of receiving aripiprazole, the neuroplasticities caused by the PCP from past usage could have contributed to his increased sensitivities and risk to developing akathisia.
PCP has been shown to cause an increased release of striatial dopamine.1 The released dopamine (DA) gives the user a sense of euphoria. PCP also blocks the dopamine transporter protein (DAT), the protein carrier responsible for re-uptaking the released dopamine back to the pre-synaptic neuron, maintaining a homeostasis and conserving dopamine reserves.2 The net result of PCP usage creates a dopamine deficit as the brain releases its dopamine endogenously during the normal courses of tonic activity without re-uptake occurring. The affected patients are in a state of diminished dopamine. This state is often associated with symptoms of hyperactivities, temperamental mood, and irritability.3
When aripiprazole, a dopamine partial agonist,4 was administered to the patient at a low dose of 5.0mg, it acted as a weak agonist and stimulated the dopamine receptors. This weak agonism, together with the brain's endogenous dopamine release, provided the proper amount of net tonic dopamine stimulation the patient needed, and the patient exhibited improvements. However, when the aripiprazole dose was increased to 10mg/day, it replaced the brain's endogenous dopamines with itself. This decreased the brain's net dopamine tonic stimulation. At the higher dose, aripiprazole acted equivalently as a net dopamine antagonist. Antagonism of dopamines increases the risk of EPS, including akathisia—a form of EPS that has been associated with aggressive behavior and suicidal potential.5
It is important to monitor EPS when prescribing medications to patients with histories of substance abuse. Aripiprazole is a very effective antipsychotic and mood stabilizer, but we must always be wary of the dual properties of aripiprazole to produce DA agonism at one dosage, yet DA antagonism at another. Being a partial agonist, the receptor dynamics between the medications and the brain's endogenous neurotransmitters could change between different dosage.
The patient actually showed a good response to a lower aripiprazole dose of 5.0mg. The akathisia seen at 10mg may not be a sign of any inherent risk factor associated with the use of aripiprazole. The history of substance abuses, in general, increases the risk factor for developing EPS, and aripiprazole, being a DA partial agonist, could produce a dynamic flux of DA homeostasis of which we clinicians must be aware.
With regards,
Tin S. Chin, MD
Assistant Professor of Psychiatry The New Jersey Medical School University of Medicine and Dentistry of New Jersey, Newark, New Jersey Phone: (973) 972-6100 E-mail: chints@umdnj.edu
References
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