Abstract

Although uncommon, the coexistence of Parkinson’s disease and bipolar disorder presents unique therapeutic challenges in both oral pharmacological treatments and the selection of device-aided interventions. Herein, we reported a 60-year-old male patient with both bipolar disorder and Parkinson’s disease. Apomorphine infusion therapy was initiated after motor symptoms remained uncontrolled despite optimized medical management. During a five-year follow-up, motor symptoms were effectively managed without any worsening of psychiatric status. Apomorphine infusion therapy may be considered a safe and effective treatment option for patients with advanced Parkinson’s disease and comorbid bipolar disorder.

Introduction

It is known that patients diagnosed with bipolar disorder have a higher risk of developing Parkinson’s disease compared to the general population.[1] In this comorbid condition, there are no guideline-based recommendations regarding medical treatment or device-aided therapy options, and the available data are limited to case reports. Antipsychotic agents and mood stabilizers, such as lithium and valproic acid, commonly used in the treatment of bipolar disorder may adversely affect patients with Parkinson’s disease.[2-4] Conversely, dopaminergic treatments used in Parkinson’s disease can trigger mania in bipolar patients, while dopamine agonists may lead to impulse control disorders (ICDs).[5,6]Device-aided treatment options are also limited in this patient group. Deep brain stimulation (DBS) is generally not preferred in cases with active psychiatric symptoms; apomorphine, as a dopamine agonist, carries the risk of triggering mania; and the use of levodopacarbidopa intestinal gel (LCIG) in psychiatric patients presents challenges, all of which restrict device-aided therapy options for this population.[7-10]

In this report, we presented a patient with comorbid bipolar disorder and Parkinson’s disease, whose motor symptoms could not be adequately controlled despite optimal medical therapy. The patient was followed for five years under apomorphine infusion therapy, during which motor symptoms were successfully managed without the occurrence of manic episodes or any worsening of the psychiatric condition.

Case Report

A 60-year-old male patient was diagnosed with bipolar disorder in 2004 and was hospitalized in the psychiatry clinic for treatment due to a mixed episode that developed two years after the initial diagnosis. In 2015, the patient presented with complaints of hand tremor and bradykinesia and was diagnosed with Parkinson’s disease at an external center. At that time, he was receiving valproic acid 1500 mg/day, quetiapine 100 mg/day, and trifluoperazine 5 mg/day, to which levodopa+benserazide 125 mg tablet (three times daily), pramipexole 1.5 mg/day, and rasagiline 1 mg/day were added sequentially. Written informed consent was obtained from patient.

In 2019, the patient was admitted to the psychiatry ward with symptoms such as excessive spending, increased activity, excessive talking, and suspiciousness and was diagnosed with a manic episode. During this period, sodium valproate and pramipexole were discontinued, and lithium 600 mg (twice daily) was initiated.

In 2020, the patient presented to our movement disorders center with a Unified Parkinson’s Disease Rating Scale (UPDRS) score of 32. Neurological examination revealed resting and postural tremor in both upper extremities, decreased finger tapping amplitude more prominent on the left side, anteflexion posture, short-stepped gait, and reduced associated movements. Following psychiatric consultation, the antipsychotic regimen was revised, and anticholinergic agents were added. However, as motor symptoms did not sufficiently improve, the dose of levodopa+benserazide was increased to 125 mg (five times daily). After the dose escalation, the patient experienced worsening hallucinations, and the regimen was reverted to the previous dose.

As the patient had become dependent in activities of daily living, an apomorphine challenge test was performed. A significant response was observed at a dose of 7 mg, with a 50% reduction in off periods and a decrease in the UPDRS score from 32 to 7. Consequently, continuous apomorphine infusion therapy was initiated at 7 mg/h for 14 h per day. During a five-year follow-up period, motor symptoms remained well controlled, and no worsening of psychiatric status or development of manic episodes was observed.

Discussion

Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, with the main therapeutic goal being the replacement of dopamine.[11] Bipolar disorder, on the other hand, is marked by manic and depressive episodes. Dopaminergic activity is thought to play a role in the pathogenesis of manic episodes.[12] Dopamine replacement, which forms the basis of treatment in Parkinson’s disease, is known to potentially trigger manic episodes, while dopamine agonists may lead to ICDs.[5,6] These interactions between therapeutic agents complicate medical management. Another critical aspect is the selection of device-aided therapies in cases with comorbid Parkinson’s disease and bipolar disorder.

In patients with Parkinson’s disease whose symptoms cannot be adequately controlled despite optimal medical treatment, device-aided therapies are considered. Apomorphine infusion therapy may be applied in individuals who have experienced side effects such as psychosis or ICDs during treatment with other dopamine agonists. However, its use is recommended with caution in patients with Parkinson’s disease with a prior diagnosis of psychosis who are under treatment and follow-up.[13] Apomorphine exerts its effects through dopaminergic, alpha-adrenergic, and serotonergic receptors. The D3 receptors in the limbic system have been associated with ICDs, while 5-hydroxytryptamine (5-HT)2A receptors have been linked to hallucinations. The low affinity of apomorphine for both D3 and 5-HT2A receptors may explain why it causes fewer ICDs and hallucinations compared to other dopamine agonists.[6,7]

In one reported case of comorbid Parkinson’s disease and bipolar disorder, even doses of pramipexole exceeding 1 mg/day were found to trigger mania.[14] Similarly, in our patient, a manic episode developed during treatment with pramipexole 1.5 mg/day, leading to the discontinuation of oral dopamine agonist therapy. Following the initiation of continuous apomorphine infusion, no manic episodes were observed throughout the five-year follow-up period.

Another device-aided treatment option is DBS. As a general principle, DBS is not preferred in patients with movement disorders who have active psychiatric symptoms. Nevertheless, case-based reports exist on the potential use of DBS in such patients. The absence of comparative groups, the low level of evidence, and the heterogeneity of the reported outcomes make clinical decision-making challenging. While the subthalamic nucleus is the most common DBS target in Parkinson’s disease, it is known that globus pallidus internus is associated with fewer neuropsychiatric side effects.[15] Therefore, globus pallidus internus DBS may represent a potential treatment option in appropriately selected patients with comorbid Parkinson’s disease and bipolar disorder.

Another device-aided therapy is LCIG infusion. In a three-year follow-up study of patients with advanced Parkinson’s disease receiving infusion therapy, both apomorphine and LCIG were found to be safe in Parkinson’s disease with ICDs. Furthermore, delivering Parkinson’s disease medications in infusion form was reported to carry a lower risk of ICD development.[9] Moreover, LCIG therapy was not only considered safe but also found to be associated with improvement in ICD symptoms.[16]

In conclusion, the comorbidity of Parkinson’s disease and bipolar disorder poses significant challenges in both pharmacological and device-aided therapeutic approaches. The bidirectional interactions between these two disorders necessitate a cautious and individualized treatment strategy in terms of both efficacy and safety. Although case reports and clinical experience are gradually increasing, the current body of knowledge remains limited. Large-scale, long-term studies are needed to develop evidence-based guidelines that can provide clinicians with a clearer direction in managing such comorbid conditions.

Citation: Büyükkoyuncu Pekel N, Yıldız D. Balancing motor control and psychiatric stability: A five-year experience with apomorphine infusion in Parkinson’s disease and bipolar disorder. Parkinson Hast Harek Boz Derg 2025;28(1):9-12. doi: 10.5606/phhb.dergisi.2025.40.

Contributed to case management, manuscript drafting, and correspondence: N.B.P.; Contributed to literature review and critical revision. Both authors approved the final version of the manuscript: D.Y.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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