Parkinson’s disease (PD) is a common degenerative disease of the central nervous system, with the main clinical manifestations being tremor, hypokinesia, tonicity, postural balance disorders, and other motor symptoms. In addition to motor dysfunction, non-motor symptoms such as different degrees of depression, anxiety and psychotic disorders are also more common, which affect patients’ quality of life, daily functioning and prognosis, and have gradually attracted attention in recent years. The incidence of depressive disorders in patients with Parkinson’s disease has been reported to be 40% to 50%, and the incidence of anxiety disorders has been reported to be 3.6% to 40.0%, and depression and anxiety disorders often coexist and can precede motor symptoms in Parkinson’s disease. The incidence of psychotic symptoms in patients with Parkinson’s disease treated with dopaminergic drugs ranged from 10% to 40%. It can be seen that depression, anxiety and psychotic symptoms are common in Parkinson’s disease, which affect the quality of life and social function of patients and increase the heavy burden of caregivers. However, clinicians in China have not paid enough attention to this issue, and there are few relevant studies. In order to better guide clinical practice and promote the progress of related research in China, it is necessary to develop suitable diagnostic criteria and treatment guidelines for depression, anxiety and psychotic disorders in Parkinson’s disease in China.
I. Clinical manifestations
1, Parkinson’s disease depression: depression can appear in all stages of the course of Parkinson’s disease, even before the appearance of motor symptoms. The degree of Parkinson’s disease depression varies, and can be major depression, mild depression, poor mood, etc.. It manifests as persistent depressed mood, difficulty concentrating, loss of interest in work and life, sleep disturbances, apathy, pessimism, lack of humor, suicidal thoughts, anxiety, and sensitivity. Self-blame, self-guilt and suicidal behavior are relatively uncommon. Those with severe cognitive impairment, women, early-onset Parkinson’s disease, and a history of depression prior to the diagnosis of Parkinson’s disease are more likely to be depressed. Depression can be manifested as “off” depression, or it can be uncorrelated with motor symptoms.
2, Parkinson’s disease anxiety: mainly manifested as generalized anxiety, panic disorder and social fear. Among them, generalized anxiety and panic disorder are more common. Generalized anxiety is mainly manifested as excessive worry, fear of death or becoming a burden to others, feeling embarrassed in public; panic disorder is mainly manifested as panic attacks, precordial discomfort, dyspnea, near-death feeling, hyperventilation, hand and foot twitching. Spacing. The anxiety symptoms are associated with postural balance disorder, and people with early onset Parkinson’s disease, anomia or “on-off” phenomenon are more likely to have anxiety. There is no clear correlation between anxiety and levodopa dose or side of onset. Anxiety is rare in people with predominantly tremors.
3. Psychotic disorder: Unlike schizophrenia or drug-induced psychotic symptoms, psychotic symptoms in Parkinson’s disease are mainly manifested as hallucinations, delusions, delusions and misconceptions of existence. Once a person with Parkinson’s disease develops psychotic symptoms, it often suggests the possibility of chronic psychosis later on, requiring more home care. Medications used to treat Parkinson’s disease may cause psychotic symptoms to occur, but more clearly correlated with the psychotic symptoms of Parkinson’s disease are the deposition of Lewy vesicles in the brain, imbalances of monoaminergic neurotransmitters, and visual-spatial processing deficits.
Hallucinations are false perceptions that occur in the absence of any stimulus and manifest as simple or complex hallucinations. Parkinson’s disease hallucinations can involve any sensory form, but visual hallucinations are the most common, and it has been reported that visual hallucinations account for more than 90% of all hallucination types in Parkinson’s disease patients. Parkinson’s disease visual hallucinations are often of vivid people or animals, but rarely of inanimate objects. Auditory hallucinations can be whispers, music, or threatening sounds, and are usually accompanied by visual hallucinations, but rarely occur alone, and can be distinguished from auditory hallucinations of schizophrenia. Other hallucinations such as tactile hallucinations, olfactory hallucinations, and gastrointestinal hallucinations are very rare, and if they occur, they are often accompanied by visual hallucinations. Parkinson’s disease hallucinations can occur intermittently, lasting from a few seconds to a few minutes each time they occur, and often recurring. Hallucinations tend to occur at night or when the patient is alone in a quiet environment.
The misperception of presence is an experience of feeling that someone or something is around when in fact that person or thing is not around at the moment and their mode of perception (e.g., auditory, visual) is not clear. A perceptual error is a false perception of a real stimulus, mostly visual. Delusions are false, solid, and unique beliefs that, despite being contrary to reality
The patient is convinced of their existence, despite being contrary to the actual situation. They are mostly paranoid, persistent beliefs, with delusions of marital infidelity and abandonment being relatively frequent. Delusions of exaggeration, somatic delusions, delusions of victimization, and religious delusions are less frequently reported.
Typical Parkinson’s disease psychotic symptoms occur mostly in patients with progressive Parkinson’s disease, often 10 or more years after diagnosis. In one study with a 5-year follow-up of 70 patients, 58 patients with typical Parkinson’s disease developed psychotic symptoms after 1 year or more on levodopa, and another 12 patients developed psychotic symptoms within 3 months of treatment with levodopa. By the endpoint of the study, all 12 patients with early onset psychotic symptoms were diagnosed with other diseases (dementia with Lewy bodies, Alzheimer’s disease, or other underlying psychiatric disorders). In contrast to the typical Parkinson’s disease late onset hallucinations, the early onset visual hallucinations were mainly threatening content visual hallucinations, mostly persisting during the day and accompanied by other types of hallucinations. This study suggests that the early onset of visual hallucinations needs to be alerted to the possibility of other diseases and requires attention to differential diagnosis.
Most patients are self-aware of the hallucinations. Depending on the presence or absence of self-awareness, hallucinations can be classified as “benign hallucinations” with self-awareness and “malignant hallucinations” without self-awareness. Benign hallucinations may be transformed into malignant hallucinations. People with drug exposure, cognitive decline, increasing age, prolonged disease duration, visual impairment, and concomitant anxiety, depression, and sleep disturbances are prone to psychotic symptoms. Psychotic disorders in patients with Parkinson’s disease can be divided into the following two categories: (1) benign psychotic symptoms: generally mild and do not have a serious impact on the patient’s life; (2) complex psychotic symptoms: hallucinations with delusions or delirium states that plague the patient and have a serious impact on life. Delirium states are mostly seen in patients with Parkinson’s disease dementia. As the disease progresses, benign psychotic symptoms can be transformed into complex psychotic symptoms.
II. Recommended screening scales
(A) Depression
Although depression in Parkinson’s disease is relatively common, depression in Parkinson’s disease is difficult to assess because of 2 factors: (1) depressive symptoms (e.g., few facial expressions, insomnia, loss of appetite, fatigue) overlap with each other and Parkinson’s disease symptoms; (2) certain patients have cognitive impairment (slow thinking, memory loss, attention loss, executive dysfunction) and have difficulty cooperating with screening.
Two prospective cohort studies found that the Hamilton Depression Inventory (17 items) was effective in evaluating depression in Parkinson’s disease, with scores greater than 13 considered depressed, with a sensitivity of 83% and specificity of 95%, and can be used for screening and severity assessment of depression in Parkinson’s disease. 1 prospective, double-blind cohort study found that the self-rating scale Beck Depression Inventory, with scores greater than 13 considered depressed, with a sensitivity of 67% and specificity of 88%.
The Beck Depression Inventory (1 level I evidence) and the 17-item Hamilton Depression Inventory (2 level II evidence) may be valid screening scales for depression in Parkinson’s disease (level B recommendation.) The Beck Depression Inventory is a self-rated scale and takes approximately lO min to score, whereas the Hamilton Depression Inventory is an other-rated scale, and scorers need to be trained accordingly and take 15-25 min to score.
(ii) Anxiety
The Hamilton Anxiety Inventory, Beck Anxiety Inventory, and Zung Anxiety Self-Rating Inventory are commonly used to examine anxiety in Parkinson’s disease, but there is a lack of high-quality double-blind controlled studies. The Beck Anxiety Inventory and the Zung Anxiety Inventory are both white-rated scales that take about 10 min to score, while the Hamilton Anxiety Inventory is an other-rated scale that requires appropriate training for the scorer and takes 15 to 25 min to score.
(iii) Psychotic symptoms
The Neuropsychiatric Inventory (NPI) is a good scale for screening patients for the presence of psychotic symptoms. The scale uses a structured interview with open-ended questions for each question, relies relatively little on rater experience, and is particularly suitable for patients with Parkinson’s disease with cognitive impairment. The Schedule for Assessment of PositiveSymptoms, Positive and Negative Syndrome Scale, and the Unified Parkinson’s Disease Rating Scale (UPDRS) Part 1 can be used for the The evaluation of psychotic symptoms in Parkinson’s disease. In addition, the Parkinson’s disease-associated psychotic symptoms questionnaire (past month; Parkinson’s disease-associated psychotic symptomsquestionnaire, questions relate to the past month) has also been reported in the literature, but all lack high-quality double-blind controlled studies to explore its sensitivity, so there is no specific recommendation for the Parkinson’s disease-associated psychotic symptoms checklist.
III. Diagnostic criteria
(A) Parkinson’s disease depression
Starkstein et al. found that patients with Parkinson’s disease were evaluated by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnostic criteria for depression, and all nine criteria related to the diagnosis of depression in the DSM-IV diagnostic criteria for depression were statistically significant by statistical analysis, suggesting that the DSM.IV diagnostic criteria for depression diagnostic criteria can be used for the diagnosis of depression in Parkinson’s disease without revision. Therefore, patients with Parkinson’s disease who present with depressive symptoms and meet the DSM-IV diagnostic criteria for depression can be diagnosed as depression in Parkinson’s disease.
1.Primary Parkinson’s disease that meets the diagnostic criteria of the British Parkinson’s Disease Association Brain Bank or the diagnostic criteria of Chinese Parkinson’s disease confirmed.
2.Meets DSM-IV diagnostic criteria for depressive episode.
A, 5 (or more) of the following symptoms within 2 consecutive weeks and a change in pre-existing function, at least 1 of which is (1) or (2), excluding symptoms apparently due to a somatic condition, or delusions or hallucinations incompatible with the state of mind. (1) Depressed state of mind almost most of the day, subjectively experienced (feeling sad or empty) or observed by others (tearfulness). Children and adolescents can be irritable. (2) Significantly less interest or enjoyment in all or almost all activities most of the day (subjectively experienced or observed by others). (3) Significant weight loss in the absence of dieting, or significant weight gain (more than 5% change in weight in 1 month), or loss or gain of appetite almost every day. Children are to be considered as not gaining weight as expected. (4) Insomnia or excessive sleep almost every day. (5) Psychomotor agitation or sluggishness (not only subjective feeling of fidgeting or sluggishness, but also observable by others) almost every day. (6) Feeling tired or lacking energy almost every day. (7) Feeling useless or having inappropriate or excessive guilt almost every day (can reach the level of delusions of guilt; not only self-blame or guilt for the illness). (8) Almost daily diminished ability to think or pay attention, or indecision (subjective experience or observed by others). (9) Recurrent thoughts of death (not just fear of death), recurrent suicidal ideation without a specific plan, or attempted suicide, or a specific plan for suicide.
B, Symptoms do not meet criteria for a bipolar disorder episode.
C, Symptoms cause clinically significant distress or impairment of social, occupational, or other important functions.
D. The symptoms are not due to the direct physiological effects of a substance (e.g., addictive drugs, prescription medications) or somatic condition (e.g., hypothyroidism).
E. The symptoms cannot be explained by a mourning reaction (i.e., a reaction to the loss of a loved one), the symptoms persist for more than 2 months, or the symptoms are characterized by significant functional impairment, pathological immersion in a sense of one’s own uselessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
Parkinson’s disease depression can be diagnosed by meeting conditions l and 2.
(ii) Parkinson’s disease anxiety
There are no clear diagnostic criteria for Parkinson’s disease anxiety. Parkinson’s disease anxiety can be diagnosed in patients with Parkinson’s disease accompanied by anxiety symptoms that meet the Chinese Classification and Diagnostic Criteria for Psychotic Disorders (3rd edition, CCMD-3) diagnostic criteria for anxiety disorders.
1.Primary Parkinson’s disease that meets the diagnostic criteria of the British Parkinson’s Disease Association Brain Bank or the Chinese Parkinson’s disease diagnostic criteria confirmed.
2.Meet the CCMD-3 diagnostic criteria for generalized anxiety, panic disorder, social phobia or obsessive-compulsive disorder (one of the four is sufficient).
(C) Parkinson’s disease psychotic disorder
Parkinson’s disease psychotic disorder can be considered if the following 1 to 5 items are met.
1. Primary Parkinson’s disease that meets the diagnostic criteria of the British Parkinson’s Disease Association Brain Bank or the Chinese Parkinson’s disease diagnostic criteria.
2.The presence of at least 1 of the following symptoms: hallucinations, delusions, delusions and the presence of misconceptions.
3.Psychotic symptoms appear after the onset of Parkinson’s disease, at least 1 year after the diagnosis of Parkinson’s disease, and mostly 10 years after the diagnosis of Parkinson’s disease.
4.Duration: hallucinations, delusions and delusions and the presence of misconceptions occur repeatedly or last for 1 month.
5. Psychotic symptoms caused by other diseases need to be excluded, such as Lewy body dementia, schizophrenia, schizophreniform disorders, affective disorders with psychotic symptoms and drug-induced psychotic disorders or delirium states.
6. Concomitant conditions: the presence or absence of self-consciousness, the presence or absence of dementia, and whether the patient is on anti-Parkinson’s disease treatment should be indicated.
IV. Treatment
This protocol is based on the implementation protocols published by the American Academy of Neurology (AAN) in 2006 on the assessment and treatment of Parkinson’s disease with depression, psychotic symptoms and dementia manifestations, and the implementation protocols published by the AAN in 2010 and the International Movement Disorders Society in 2011 on the treatment of non-motor symptoms, combined with evidence-based medicine in recent years.
(I) Treatment principles
1.Patients with depression and anxiety in Parkinson’s disease should undergo antidepressant and anxiety treatment to improve the quality of life.
If patients with Parkinson’s disease develop psychotic symptoms such as hallucinations and delusions, they should consider reducing or discontinuing benzhexol, amantadine, dopamine agonists or monoamine oxidase-B inhibitors in order; if symptoms still improve, levodopa should be gradually reduced; if symptoms or extrapyramidal symptoms deteriorate despite the above measures, it is appropriate to choose non-classical antipsychotic drugs with definite efficacy and low extrapyramidal adverse effects. If symptoms or extrapyramidal symptoms deteriorate despite the above measures, it is advisable to choose non-classical antipsychotic drugs with high efficacy and low extrapyramidal adverse effects, and strive to obtain the best efficacy with the smallest dose.
3. Dopamine replacement therapy and antipsychotic treatment are a contradiction, the improvement of one symptom may lead to the worsening of another symptom, the principle to be followed in treatment is to control motor symptoms with the least possible dopaminergic drugs and psychotic symptoms with the lowest dose of antipsychotic drugs.