Case study on the treatment of dopamine dysregulation syndrome

1. Introduction

Dopamine dysregulation syndrome (DDS) is a common clinical motor and behavioral dysfunction disorder. Several studies have been conducted on DDS in clinical practice [1]. Current clinical healthcare workers mainly hold that DDS is a balance disorder with hedonistic chemicals that cause patients to get sick. During clinical treatment, patients will suffer because of drug abuse or drug addiction [2, 3]. Dopamine replacement therapy (DRT) is generally used as the main clinical treatment method. However, after long-term treatment, patients will develop tolerance after persistent high mood. Drug withdrawal will cause patients to experience hypothymic depression and even cycling affective disorder in severe cases, affecting their daily work and life [4]. Therefore, a patient with DDS treated in our hospital was evaluated in this study, and a systematic study was performed on the treatment regimen of the patient to establish a safe and effective treatment regimen for DDS.

2. Case report

(1) Basic information: The patient was 55 years old and had a medical history of 14 years. He suffered from the onset with bradykinesia and hand tremors that could be controlled by medication. After that, the patient had a DBS operation (the specific target was unknown) four years ago due to negative side effects and dyskinesia. Before the operation, the patient took Madopar 250 mg 5–6 times a day and Trastal 50 mg TID. After the operation, the patient took Madopar 125 mg QID and Trastal 50 mg BID.

(2) The conscious effect decreased significantly in the past year, with the main manifestations being a feeling of dizziness and fullness in the head and back pain, lower back pain. The patient adjusted the dose of Madopar and Sinemet to one tablet each time, 7–8 times a day, and Trastal to 50 mg TID without medical advice. This oral administration caused the patient to experience obvious abnormal movement, which seriously affected him, but he could walk by himself without falling. The abnormal movement was relieved about three hours after oral administration, but the patient experienced systemic pain, chest distress, suffocation, and restlessness. He complained that he felt insobriety, a swollen head, and a feeling of dizziness, but he could still walk. The patient had an uncontrollable desire to take the medicines, and the pain could be relieved after oral administration. He also experienced poor sleep, difficulty falling asleep, and significant weight loss. In the last six months, his weight decreased by about 15 kg.

(3) History of treatment: The patient went to a psychiatric hospital and used Quetiapine, Citalopram, and other drugs, but the symptoms did not improve significantly. (4) Relevant scale scores [5]: MDS-UPDRS III score (ON stage) was 10 points; MDS-UPDRS III score (OFF stage) was 10 points; MDS-UPDRS I score was 25 points; H-Y rating score (ON stage) was 2 points; H-Y rating score (OFF stage) was 2 points; MMSE score was 29 points; MOCA score was 27 points; HAMA score was 29 points; HAMD score was 28 points. (5) Auxiliary examinations: no significant abnormality was found in brain magnetic resonance imaging. Bladder residual urine examination showed no abnormality. The chest computed tomography and color Doppler ultrasonography of the liver, gallbladder, pancreas, spleen, and kidney showed no significant abnormalities. The ceruloplasmin tests showed normal levels, and no abnormality was found in the routine blood, coagulation, biochemistry, blood homocysteine, folic acid, vitamin B12, tumor marker, or erythrocyte sedimentation rate tests or in the spectrum of antinuclear antibodies.

Clinically, we established a safe and effective treatment regimen for the patient according to his clinical symptoms: (1) withdrawal of Trastal; (2) gradually decreasing the dose of Madopar to 0.25 tablets QID; (3) adding Comtan 0.1 g BID; and (4) adding clozapine 12.5 mg QN and gradually increasing the dose to 25 mg QN.

Dopamine dysregulation syndrome has specific clinical diagnostic criteria: (1) Parkinson’s disease (PD) with documented levodopa responsiveness; (2) the need for increasing doses of levodopa in excess of those normally required in clinical treatment; (3) a pattern of pathological use: expressed need for increased DRT in the presence of excessive and significant dyskinesias despite being “on;” (4) an unwillingness to reduce DRT; (5) an absence of significant painful dystonias; (6) an impairment of social or occupational functioning: fights, violent behavior, loss of friends, absence from work, arguments or difficulties with family; (7) the development of manic and bipolar affective syndrome in relation to DRT; and (8) a duration of disturbance of at least six months.

After applying the new clinical treatment regimen, the patient’s body dopamine index gradually normalized. The clinical return visit to the patient revealed that if such a treatment regimen was maintained for a long time, his body function would stabilize in the process of clinical prognosis. The medication inspection of the patient during treatment revealed that he did not experience any negative side-effects in long-term treatment. While effectively improving the clinical symptoms of patients, the new treatment regimen can effectively improve the quality of life of patients and has high clinical application value.

3. Discussion

Basal ganglia are the main site of obsessive-compulsive behavior disorders in clinical patients. When patients have PD, they experience obsessive-compulsive and impulsive behaviors [6]. According to relevant clinical data, patients with PD will have impulse control disorders that cause neuropathy in the absence of effective follow-up treatment, affecting their health. In addition, the dose of dopamine drugs should be strictly controlled during treatment to control the onset of the disease. During clinical treatment, pathological gambling (if any) is related to the use of dopamine receptor agonists, and doses of levodopa that are too high will cause hypersexuality [7]. Studies show that clinical patients who have issues with pathological gambling or compulsive buying are strongly correlated with the application of different doses of levodopa, and the use of levodopa and other drugs will cause patients to have habitual, repetitive behaviors. In addition, habitual, repetitive behavior is also related to the clinical use of excessive doses of Quetiapine, a dopamine antagonist. The pathogenesis is that lengthy oral administration of dopamine drugs will lead to an abnormal release of dopamine in patients’ bodies [8]. This is similar to the reward theory, when the ventral tegmental area (VTA) of a patient’s midbrain projects to the nucleus accumbens (NAc), which receives projections from the amygdala (AMG), hippocampus, motor cortex, premotor cortex, cingulate gyrus, and prefrontal cortex at the same time, and they constitute a reward circuit. Clinical application of DRT to patients may cause sensitization of the VTA in the patient’s body, thus improving the dopamine level in the NAc, making patients feel happy during clinical treatment. The treatment gradually becomes necessary, and patients are prone to addiction in the long-term treatment process [9]. Levodopa may induce more dopamine release than is natural in the patient’s body, becoming an expected reward that is processed and strengthened by dopaminergic neurons in the patient’s mesolimbic system and then projected to the hippocampus and AMG through the learning and memory process of the NAc, making the medication behavior a habitual stimulus. In the course of clinical treatment, DRT will involve the relevant pathway system in the patient’s body to supplement dopamine to achieve normal dopamine levels.

Drug addiction behavior is the main behavior disorder of patients with PD. When patients with PD take dopamine drugs for a long time, these drugs can improve the patients’ motor symptoms, thus improving their psychological state. Therefore, clinically, unhealthy emotions of patients with PD will cause patients to take excessive dopamine drugs and then form drug addiction [10].

4. Conclusion

This study shows that in the treatment process of DDS, the dose of dopamine drugs should be strictly controlled and follow the principle of “using the minimum drug dose to achieve the best clinical treatment effect.” The treatment regimen for PD should be optimized to use long-acting dopamine receptor agonists or intestinal infusions rather than a short-acting levodopa preparation and subcutaneous injections of apomorphine. According to this study’s results, the combination of antipsychotics and antidepressants in the future clinical treatment of PD can avoid drug addictions; this has high clinical value.

Funding

None to report.

Informed consent

Written informed consent was obtained from the participant for the publication of this case report (including all data).