Antipsychotics are the first-line treatment for psychotic disorders, which have antagonistic effects on the D2 dopamine-receptor, reducing dopamine mediated transmission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) defines tardive dyskinesia as a medication-induced movement disorder that persists despite discontinuation or change of the medications.[1] The disordered movements seen in tardive dyskinesia (TD) are thought to be caused by the blockade of D2 dopamine-receptors. The movement disorders include akathisia, dystonia, buccolingual stereotypy, chorea, tics, and other abnormal involuntary movements of the face, mouth, jaw, and extremities.[2] Most often, these dyskinetic disorders precipitate following chronic antipsychotic administration, however, there are reported cases of patients developing symptoms consistent with TD after withdrawal of antipsychotic medications.[3]
Supersensitivity psychosis (SP) was first defined as the emergence of psychotic symptoms with tardive dyskinesia and a decrease in prolactin levels following the discontinuation of certain medications. In the context of antipsychotics, there are four main clinical characteristics used to define medication-induced SP, including: 1) rapid relapse of symptoms following the discontinuation, dosing change, or a change in antipsychotic medication; 2) new onset tolerance after previously having therapeutic effects; 3) presence of TD; and 4) psychotic exacerbations due to life stressors. Additionally, in order to diagnose SP, a patient must also have been taking an antipsychotic for 3 months. It is hypothesized that what was previously described as “treatment resistant schizophrenia” is in fact SP, with SP being observed in 70% of treatment-resistant schizophrenic patients versus 30% in non-treatment resistant patients.[4]
Second-generation antipsychotics (SGAs) are widely used to treat a variety of psychotic symptoms, having largely replaced first-generation antipsychotics (FGAs) due to their more favorable side effect profile. Psychosis is believed to be due to excess dopamine signaling in the striatum, therefore both FGA and SGA work by blocking dopamine transmission in the striatum via the dopamine D2 receptors.[5] The D2 receptor is important with its involvement in SP, as antipsychotics are antagonists of this receptor postsynaptically.[6] It has been shown that the D2 receptor is prone to plasticity and remodeling. The effect of prolonged antipsychotic use on the intracellular system leads to an increased number of postsynaptic D2 receptors within the striatum, leading to hypersensitivity over time.[4]Our patient had been receiving chronic antipsychotic treatment for schizoaffective disorder for several years prior to her admission to the hospital. Therefore, it can be postulated that at this time she would have had an increased density of dopamine receptors in her striatum, which would have put her at increased risk for SP. Shortly after a change to her medications, she developed TD symptoms such as lip-smacking, which was not experienced previously. This illustrates the possibility that our patient was experiencing SP due to prolonged use of her antipsychotics, which led to negative symptom development when her mediations were adjusted. As studies have demonstrated previously, as patients continue to take antipsychotics, the density of these receptors increase causing the need for increased levels of antipsychotics in order to control the increased dopamine levels to maintain symptom control.[7] This further perpetuates tolerance and increases the risk for SP.[4]
Similar to our case, another case report described a female patient who experienced TD after being abruptly withdrawn from risperidone, with resolution of symptoms occurring after starting a new antipsychotic medication. While TD can occur in all ages, it has been shown to be most common in elderly patients, particularly elderly female patients.[8] The patient we presented in this case was an elderly female, and given the previous findings of high-risk of TD and SP in this age group, greater care and monitoring should be taken when adjusting antipsychotic medications.
Due to the risk of severe psychosis and TD, it has been proposed that intermittent dosing, use of long-acting antipsychotics, and controlled tapering can help prevent SP. Furthermore, it is widely accepted that SGAs are less likely to invoke supersensitivity and drug-induced movement disorders when compared to FGAs, and therefore are the preferred first choice of medication when treating psychosis.[4] With this being said, many studies suggest the use of long-acting injectables, such as risperidone to prevent and reduce the incidence of SP.[4,9] A 12-month study evaluating treatment resistant patients (TRP) and dopamine supersensitivity patients (DSP) found that DSP had a significant improvement of symptoms while on long-acting risperidone, when compared to TRP. DSP patients at baseline had more severe extrapyramidal symptoms, however they had a 62% higher response rate to long-acting risperidone compared to 21% of non-DSP patients.[9] The long-acting and high-potency injectables have shown to stabilize the receptors and minimize fluctuations of dopamine, thereby decreasing the incidence of SP.[4]
When considering treatment for the symptoms of SP, medications should aim to reduce the increase in D2 receptor density. One study suggests the use of anti-seizure medications such as valproate, carbamazepine, or phenytoin. The early addition of these medications with an antipsychotic has shown to potentiate the effects of the antipsychotic, thereby reducing the need for increased doses, and decreasing the likelihood of the patient developing SP.[10] Electroconvulsive (ECT) therapy has also illustrated the ability to normalize the density of D2 receptors, which was also found with our patient who had resolution of her catatonia after eleven ECT treatments.[4]
Another possible treatment option is the use of clozapine for SP symptoms. A study of 15 patients experiencing SP symptoms found that 13 of the 15 patients experienced no further SP symptoms after the initiation of clozapine for the duration of the 2.65 year follow-up.[11] The efficacy of clozapine on SP symptoms has been thought to be due to its role on GABAergic neurons and its potency on D2 receptors, however, this has not been clearly defined. Initially, our patient had no symptom relief upon starting Clozapine 25 mg once daily, but upon increasing the dose to twice daily dosing and tapering down off risperidone, her TD symptoms improved within six days. While our patient did not have complete resolution of her TD symptoms, she did experience symptomatic improvement. It is shown that only 33% of patients will have complete resolution of TD symptoms within two years, so it was not expected for her to have had complete resolution of the symptoms during our time frame of care for her.[3]