A first-hand experience highlights how important it is to be alert for unusual antipsychotic side-effects.
Aside from treating psychosis and mania, antipsychotic medications are known to be helpful for other conditions such as anxiety, insomnia and nausea.
In this article, I aim to describe both the context of extrapyramidal side effects at low doses of antipsychotic medication and the actual experience of dystonia so that prescribers can better understand symptoms that patients describe that may not currently raise suspicion of extrapyramidal side effects.
Case presentation
I am a 36-year-old psychiatry registrar and have been experiencing depressive episodes with agitation for the past year. I have no family history of neurological disorders.
I do have Ehlers-Danlos Syndrome, Type III, however, which can affect medication metabolism and often makes me more sensitive to side-effects.
With Ehlers-Danlos Syndrome, I experience a lot of joint pain, including my shoulders and neck that can trigger migraines.
Treatment includes duloxetine and repetitive transcranial magnetic stimulation for depression, among other medications for physical issues that do not have known interactions with antipsychotic medications or serotonergic properties.
I have had two attempts at antipsychotic augmentation to help with intrusive thoughts and associated distress.
In the first instance, I experienced tongue tremor and speech difficulties with 1.25mg olanzapine for about 24 hours following each dose.
Quetiapine was trialled on the basis that extrapyramidal side effects are thought to be rare with this medication compared with other antipsychotics. While brexpiprazole is not known to cause extrapyramidal side effects, the risk of increasing agitation with brexpiprazole made it unacceptable.
An acute dystonia was experienced after two days of taking 50mg quetiapine IR at night following three days of taking 25mg at night. There had been no extrapyramidal side effects as a result of duloxetine, which had been taken for approximately eight months prior to this episode.
Leading up to the dystonic reaction, there were no obvious extrapyramidal side effects. There had been increased shoulder and neck pain and generalised joint pain, which, at the time, I attributed to normal fluctuations of Ehlers-Danlos Syndrome symptoms.
However, one night I was woken by severe spasm and pain in my right bicep and neck. I could not straighten my arm. There appeared to be no problems with my left arm.
The dystonia was relieved with 2mg oral benzatropine, and the quetiapine was ceased.
Over the next 24 hours, both arms felt sore and “fatigued”. I had cogwheeling in my right arm. In the 48 hours following the last dose of quetiapine, symptoms gradually resolved.
Brexpiprazole augmentation was later trialled starting at 0.5mg each morning and titrated to 2mg with no agitation or extrapyramidal side effects.
Discussion
Metabolic differences in Ehlers-Danlos Syndrome are poorly understood, however some drugs have been observed to commonly have poor efficacy in Ehlers-Danlos Syndrome patients. For example, lignocaine (lidocaine) may have reduced or no effect as a local anaesthetic. Little is known about the mechanism for such differences in drug metabolism.
Typically, we expect unilateral tremor or dystonia to be associated with early Parkinson’s disease rather than extrapyramidal side effects, and a neurological opinion may be indicated if the potential causative agent cannot be safely withdrawn to test causation.
While antipsychotic medications largely are inverse agonists of D3 in the treatment of positive symptoms in psychosis, 5HT-2A antagonism is considered instrumental in treatment of negative symptoms.
Extrapyramidal side effects are thought to be mainly due to inverse agonism of D2 receptors, while there may be some role of cholinergic activity. Quetiapine acts as an antagonist of the 5HT-2A receptor with reduced binding of the D2 receptor and is often thought not to be associated with extrapyramidal side effects. Other serotonergic agents such as antidepressants, especially duloxetine, have also been associated with extrapyramidal side effects.
My experience highlights the potential for extrapyramidal side effects with unexpected medications as well as mild or unusual symptoms of extrapyramidal side effects as a potential harbinger of more severe reactions.
Potential metabolic differences in special populations can create an unfavourable situation for side effects.
More research is needed on the role of the serotonin system in extrapyramidal side effects and greater awareness of the potential for them in serotonergic medications.
Dr Israel Berger is a psychiatry registrar with the Child and Adolescent Mental Health Service, Goulburn Valley Health, in Shepparton, Victoria.
