Treatment Of Depression In Parkinson's Disease Research Articles

Acupuncture inhibits autophagy and repairs synapses by activating the mTOR pathway in Parkinson’s disease depression model rats

Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of ɑ-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.

Depression in Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a progressive neurodegenerative age-related disorder that affects the central nervous system (CNS) and is characterized by uncontrollable movements such as shaking, stiffness, and loss of balance and coordination. Depression is a common non-motor manifestation of PD, but unfortunately, depression remains unrecognized and often undertreated. The underlying pathophysiology of depression in PD is complicated, and many studies have been conducted to know the exact cause, but the question remains unanswered.In this article, we discuss various pathophysiologies by which depression occurs in PD. The most widely accepted theories are neuroinflammation and monoamine oxidase theory. This article also explored the pharmacological treatment of depression in PD; this involves standard antidepressant therapy such as tricyclic antidepressants (TCA), serotonin-norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), and monoamine oxidase inhibitors (MAO); non-pharmacological treatments such as electroconvulsive therapy (ECT), cognitive-behavioral therapy (CBT) have also been discussed. However, physicians hesitate to prescribe antidepressants to patients with PD due to concerns about harmful drug-drug interactions between antidepressants and antiparkinsonian drugs. Despite the complicated link between PD and depression, the co-administration of antidepressants and antiparkinsonian drugs is safe and beneficial when appropriately managed. However, early recognition and initiation of treatment of depression in PD reduces the longitudinal course and improves the cross-sectional picture. This review article also explored the clinical and diagnostic findings and impact on the quality of life of depression in PD.

Efficacy and tolerability of antidepressants in Parkinson's disease: A systematic review and network meta-analysis.

To systematically review and analyze the efficacy and tolerability of different antidepressant pharmacologic treatments for depressive symptoms in Parkinson's disease (PD) METHODS: We searched PubMed, EMBASE, Cochrane database (CENTRAL), clinicaltrials.gov, and bibliographies for randomized controlled trials investigating the efficacy of antidepressant medications versus a non-treatment, placebo, or active treatment groups for depressive symptoms in PD. Twenty of 3191 retrieved studies (1893 patients) were included, but not all could be meta-analyzed. We used a random-effects model meta-analysis to compare depression scores between an active drug and placebo or control group then used a network meta-analysis to compare the effectiveness of different antidepressant classes. The primary outcome was the efficacy of different classes of antidepressant medications in PD patients with depressive symptoms, measured by standardized mean difference (SMD) in depression score from baseline compared with control. Pairwise meta-analysis suggested that type B-selective monoamine oxidase inhibitors (SMD=-1.28, CI=-1.68, -0.88), selective serotonin reuptake inhibitors (SMD=-0.49, CI=-0.93, -0.05), and tricyclics (SMD=-0.83, CI=-1.53, -0.13) are effective antidepressants in PD. Network meta-analysis showed that monoamine oxidase inhibitors had the largest effect on depression in PD (SMD (vs selective serotonin reuptake inhibitors)=-0.78, CI=-1.55, -0.01), but these might not be considered traditional antidepressants given their type B selectivity. Although limited by few data, this review suggests that multiple antidepressant classes are potentially efficacious in the treatment of depression in PD, but that further comparative efficacy and tolerability research is needed.

Use of antidepressants in Parkinson's disease: A Swedish register-based study of over 1.5 million older people

IntroductionIt has been suggested that depression in Parkinson's Disease (PD) is often unrecognized and undertreated. However, few previous studies have studied the use of antidepressants in a large sample of both home-dwelling and institutionalized elderly persons with PD. We aimed to study the use of antidepressants in older persons using anti-parkinson drugs (APD, used as a proxy for PD), stratified by residential setting. MethodsWe analyzed individual data on age, sex, residential setting and drug use in over 1.5 million older persons in the Swedish Prescribed Drug Register on 31th of December 2013. ResultsTwenty-two percent of the home-dwellers and 50% of the institutionalized elderly persons with APD used antidepressants. Persons with APD had a higher probability of use of any antidepressant compared to persons without APD. A selective serotonin reuptake inhibitor (SSRI) was the most commonly used antidepressants in both settings followed by mirtazapin. ConclusionsThe high use of antidepressants among older persons with APD warrants further studies on the quality of treatment of depression in PD.

Electroconvulsive therapy for depression in Parkinson's disease: systematic review of evidence and recommendations.

We performed a systematic review of evidence regarding treatment of depression in Parkinson's disease (PD) utilizing electroconvulsive therapy. The search led to the inclusion of 43 articles, mainly case reports or case series, with the largest number of patients totaling 19. The analysis included 116 patients with depression and PD; depression improved in 93.1%. Where motor symptoms' severity was reported, 83% of patients improved. Cognition did not worsen in the majority (94%). Many patients experienced delirium or transient confusion, sometimes necessitating discontinuation of electroconvulsive therapy (ECT). Little is known about maintenance ECT in this population. ECT can benefit patients suffering from PD and depression. We recommend an algorithm for treatment of depression in PD, utilizing ECT sooner rather than later.

Neuropsychiatric Symptoms in Parkinson's Disease.

Parkinson's disease (PD) is characterized by motor symptoms, but focused and extensive research in the last years has provided new knowledge in the field of non-motor symptoms. Non-motor symptoms include neuropsychiatric symptoms such as depression, anxiety, psychosis, apathy, impulse control disorders, and occur in the majority of patients with PD. They are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies commonly used for treatment of PD can induce or worsen such symptoms. This paper discusses the epidemiology, clinical features and treatment approaches for neuropsychiatric symptoms (NPS) in PD in the perspective of clinical practice and management. The prevalence rates of various NPS are high, various demographic, clinical and treatment related variables have shown to be associated with higher risk of NPS. Randomized controlled trials of pharmacological and non-pharmacological treatments of NPS in PD are sparse. Current evidence supports tricyclic antidepressants as efficacious treatment of depression in PD and antipsychotic clozapine as efficacious choice for psychosis. Further studies to evaluate various other management strategies of NPS in PD are required. Neuropsychiatric symptoms in PD should be considered an integral part of the disease; hence a multidisciplinary approach is essential to improve the overall outcome of PD also through raised awareness and enriched knowledge on NPS.

Systematic review of traditional chinese medicine for depression in Parkinson's disease.

Depression is the most common non-motor symptom of Parkinson's disease (PD). Recent clinical trials have evaluated the effectiveness of traditional Chinese medicine (TCM) in the treatment of depression in PD (dPD). However, the results are conflicting rather than conclusive. To investigate the effectiveness of TCM for the treatment of dPD, a systematic review was conducted. Literature searches and collections were performed to identify studies addressing the treatment of TCM for dPD. The methodological quality and risk of bias in all studies included were evaluated. Weighted mean difference (WMD) with 95% confidence interval (CI) was used as the effect measure. Finally, a total of 10 studies involving 582 patients were identified. The pooled results revealed that TCM combined with conventional drugs significantly improved the total scores of the unified Parkinson's disease rating scale (WMD = -7.35, 95% CI: -11.24 to -3.47) and the score of the Hamilton rating scale for depression (HAM-D) (WMD = -4.19, 95% CI: -5.14 to -3.24) compared with conventional drug, respectively. Conclusively, there is evidence that TCM may be beneficial to the treatment of dPD in spite of the methodological weakness of the included studies.

Comparative Efficacy and Acceptability of Antidepressants in Parkinson's Disease: A Network Meta-Analysis

BackgroundDepression is a common non-motor symptom in patients with Parkinson's disease (PD). There are many kinds of antidepressants being used, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and Dopamine agonists which are suggested as alternative antidepressants for the treatment of depression in PD. Which one should we choose first? Literatures have shown inconsistent results.MethodsWe conducted a network meta-analysis of randomized controlled trials to compare the efficacy and acceptability of therapeutic methods for the treatment of depression in Parkinson's disease.ResultsWe used the odds ratios (OR) as effect size firstly and the results indicated no statistical significance between each compared intervention. Then we used the logarithm of the individual odds ratios as effect size. With efficacy of TCAs as the standard of comparison, the degree of incoherence (a measure of how closely the entire network fits together) was small (ω = 4.824827e-05). The logor were: SSRIs −0.69 (95% CI −1.28– −0.10); Pramipexole −0.73 (−1.71– −0.26); Pergolide −1.97 (−3.67– 0.27); SNRIs −0.86 (−1.86– 0.15); Placebo −1.24 (−1.99– −0.50). With Placebo as the standard of comparison, the logor were: TCAs 1.24 (0.50– 1.99); SSRIs 0.55 (−0.03– 1.13); Pramipexole 0.51 (−0.12– 1.15); Pergolide −0.73 (−2.25– 0.80); SNRIs 0.38 (−0.42– 1.19); TCAs, pramipexole, pergolide and SNRIs showed better profile of acceptability, leading to significant fewer discontinuations than that of SSRIs.ConclusionsThere is insufficient evidence to support antidepressant efficacy for SSRIs, pramipexole, pergolide and SNRIs. TCAs might be the best choice when starting antidepressant treatment in patients of Parkinson's disease because it has the most favorable balance between benefits and acceptability, followed by pramipexole and SNRIs, SSRIs might be the last choice.

MAO-inhibitors in Parkinson's Disease.

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.

Depression in Parkinson's Disease: Symptom Improvement and Residual Symptoms After Acute Pharmacologic Management

Parkinson's disease (PD) is frequently complicated by depression and there is a paucity of controlled research that can inform the management of this disabling nonmotor complaint. A randomized controlled trial of nortriptyline, paroxetine, and placebo for the treatment of depression in PD (dPD) was recently completed. The purpose of this article is to describe the baseline pattern of depressive symptom presentation in PD, the specific symptoms of dPD that improve with pharmacotherapy, and the residual symptoms that remain in patients who meet a priori criteria for response or remission after acute treatment (8 weeks). The Departments of Psychiatry and Neurology at Robert Wood Johnson Medical School, New Jersey. : Fifty-two depressed patients (major depression or dysthymia based on Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) with Parkinson's disease (by research criteria). A randomized controlled trial of nortriptyline, paroxetine, and placebo. The four subscales (core mood, anxiety, insomnia, and somatic) and individual items from the Hamilton Rating Scale for Depression-17 were the focus of this study. These measures were assessed at baseline and Week 8. Baseline depressive symptoms were unrelated to motor functioning. Treatment response was associated with significant improvements in the core mood, anxiety, insomnia, and somatic symptoms seen in dPD. Residual symptoms, such as sadness and loss of interest, persisted in treatment responders in a milder form than was initially present. Antidepressants may influence all symptoms of dPD, including those that share great overlap with the physical disease process. Additional research regarding adjunctive interventions is needed to help optimize the management of dPD.

The Role of Dopamine Agonists in the Treatment of Depression in Patients with Parkinsonʼs Disease

Depressive disorders as well as depressive symptoms are common in Parkinson's disease (PD) and an important factor affecting quality of life. Treatment of depressive symptoms not only improves mood but is also associated with improvement of motor symptoms, disability and cognitive symptoms. Currently, dopamine agonists are being suggested as an alternative to antidepressants for the treatment of depression in PD. The aim of this article is to systematically review the efficacy of dopamine agonists in the treatment of depression in PD. Since 1983, 19 studies have reported on the effects of dopamine agonists on depressive disorder, depressive symptoms or mood in PD. To date, no double-blind, placebo-controlled, randomized controlled trial of the treatment of major depressive disorder in PD with a dopamine agonist has been conducted. Studies of the effects of treatment with dopamine agonists on depressive symptoms in PD, or on mood in non-depressed PD patients, have yielded inconclusive results. Most studies are not designed to test effects on mood and are limited by methodological flaws. It can be concluded that, although the preliminary evidence of the effects on mood and depression in PD is interesting and in need of further study, there is as yet insufficient evidence to recommend dopamine agonists in the treatment of either depressive disorder or depressive symptoms in patients with PD. Treatment of depressive disorder and clinically relevant depressive symptoms should be based on pharmacological or non-pharmacological interventions with known efficacy in this population, such as citalopram, nortriptyline, desipramine or cognitive behavioural therapy. This strategy has the additional advantage of enabling the clinician to treat depressive symptoms independently of motor symptoms, thus avoiding potential complications of dopaminergic therapy.

Bupropion in the treatment of depression in Parkinson's disease

A 78-year-old female with a nine-year history of depression was hospitalized due to worsening depression and symptoms associated with Parkinson's disease (PD). Her motor abilities improved on levodopa and the depression improved after a trial of bupropion, following unsuccessful treatment with other antidepressants. We found four reports on successful treatment of depression in PD with bupropion. However, no controlled double-blind studies have been conducted so clinicians should be cautious when administering bupropion in depression in PD.

Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants for the treatment of depression in patients with Parkinson's Disease (PD) but data on their efficacy are controversial.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials to investigate the efficacy and acceptability of SSRIs in the treatment of depression in PD.ResultsTen studies were included. In the comparison between SSRIs and Placebo (n = 6 studies), the combined risk ratio (random effects) was 1.08 (95% confidence interval: 0.77 - 1.55, p = 0.67). In the comparison between SSRIs and Tricyclic Antidepressants (TCAs) (n = 3 studies) the combined risk ratio was 0.75 (0.39 - 1.42, p = 0.37). An acceptability analysis showed that SSRIs were generally well tolerated.ConclusionsThese results suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in PD. Due to the limited number of studies and the small sample sizes a type II error (false negative) cannot be excluded. The comparison between SSRIs and TCAs is based on only three studies and further trials with more pragmatic design are needed.

Coaxil (tianeptine) in the treatment of depression in Parkinson’s disease

An open, non-comparative clinical study was performed to assess the efficacy and safety of tianeptine (Coaxil) in Parkinson's disease (PD). A total of 18 patients with PD were used whose clinical state increased moderately severe and more profound depression (assessed on the Hamilton and Beck scales). After three months of treatment, depression on the Hamilton depression scale was decreased by 34% and on the Beck scale by 31% compared with baseline data ((p) < 0.05). Improvements in mental status were noted in 14 of 18 patients (77%); eight patients (44%) showed more than 50% reductions on the Hamilton scale. Analysis of the structure of depressive symptomatology showed that improvement occurred because of decreases in anxiety and the severity of somatoform symptoms and, to a lesser extent, in melancholy and sleep disturbance. There was no significant change in apathy. The decrease in the severity of depression was accompanied by an improvement in the quality of life. The efficacy of Coaxil was greater in patients with less marked depressive and motor symptoms, shorter durations of illness, and less marked cognitive impairments. Coaxil was well tolerated by the patients. The data obtained here provide grounds for recommending the use of Coaxil in the treatment of depression in PD.

Prevalence and Treatment of Depression in Parkinson’s Disease

Parkinson's disease (PD) is a progressive neurological condition with debilitating symptoms, and depression is a common comorbid condition of this disease. The authors review existing literature on the prevalence and treatment of depression in PD. Prevalence estimates of depression vary widely, ranging from 7%-76%. This variation is due to inconsistent methodology. Treatment options for depression in PD include medication therapy, electroconvulsive therapy (ECT), and psychotherapy. There are few randomized controlled trials of these treatment options. The authors argue for more systematic and controlled research examining both the prevalence and treatment of depression in PD.

Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1)

Depression is a common symptom in Parkinson's disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT)n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet (AAT)n of the gene that encodes CB1 (CNR1) receptor in 89 subjects (48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression (Fisher's exact test: P=0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.

Mental and Behavioral Dysfunction in Movement Disorders

Mental and Behavioral Dysfunction in Movement Disorders

Depression in Parkinson's disease.

Depression in Parkinson's disease (PD) is a common complication, with a major impact on quality of life. Failure to recognize and treat depression can lead to premature and inappropriate discontinuation of antiparkinsonian therapies. Cited frequency for depression in PD varies between 2.7 and 70%. Methodological differences account for much of the disparity. The aetiology of depression in PD is complex, with 'tonic' (slowly changing and persistent) and 'phasic' (short-lived and fluctuating) components. Both depression and anxiety may predate the onset of the motor disorder by some years. Hedonistic homeostatic dysregulation is a cyclical mood disorder associated with excessive intake of dopaminergic therapies, inappropriate for the motor state. Negative affective symptoms occur on attempted reduction of medication, reinforcing the abnormal medication pattern. The Montgomery-Asberg Depression Rating Scale and the Hamilton Rating Scale for Depression have good diagnostic sensitivity and specificity for assessing depression in PD. There is a dearth of sizeable, placebo-controlled studies for evaluating drug treatment of depression in PD. Dopaminergic drugs have variable antidepressant properties. Selective serotonin reuptake inhibitors are currently the most commonly prescribed group of antidepressants in the depressed PD patient. Depression in the PD patient may be associated with a more rapid deterioration in cognitive and motor functions.

Beyond the iron mask: towards better recognition and treatment of depression associated with Parkinson's disease.

This review examines the frequency of depression complicating Parkinson's disease (PD), its aetiology and clinical features, and also how it may be recognised and treated. Studies investigating the frequency of depression in PD have yielded figures ranging between 2.7% and 70%. Methodological differences account for much of the disparity. The aetiology of depression in PD is complex, and probably relates to both biological and exogenous factors. Dysfunction of multiple neurotransmitter systems, including the serotonergic system, may be involved. Mood disturbances resulting from deep brain stimulation of the subthalamic nucleus may provide a fruitful area for future research, and assist our understanding of the neural networks involved in mediating depression. Several recent studies have confirmed that depression in the PD patient is a major determinant of quality of life and that this is closely related to dysfunction in other clinically important health areas. The validity for many existing scales in the screening, diagnosis, and monitoring of depression in the PD patient has not been established. The Montgomery-Asberg Depression Rating Scale and the Hamilton Rating Scale for Depression appear to have good diagnostic sensitivity and specificity when compared with DSM-IV criteria. Recommendations for the optimal drug treatment of depression in PD are difficult to give, due to an inexplicable dearth of sizeable, placebo-controlled studies. A majority of physicians would probably now opt for a selective serotonin reuptake inhibitor in the depressed PD patient. There is no good evidence that these drugs are associated with a worsening of motor features, but they should probably not be coprescribed with selegiline, because of the risk of causing a potentially serious serotonin syndrome. Several studies have suggested that depression in the PD patient is associated with a more rapid deterioration in cognitive and motor functions, perhaps as a surrogate marker for more extensive brainstem cell loss.

Current Issues in Depression in Parkinson's Disease

Depression affects 40%-50% of Parkinson's disease (PD) patients. The authors, by use of a Mednet and manual search of pertinent literature, summarize current issues in the treatment of depression in PD. Open-label studies suggest that antidepressants may be effective for treating depression in PD. Although case reports indicate that selective serotonin reuptake inhibitors (SSRIs) can potentially worsen the motor symptoms of PD, this effect has not been confirmed in the small number of open-label studies that have been performed to date. The occurrence of the serotonin syndrome resulting from a combination of selegiline and an SSRI appears to be rare. Double-blind prospective studies are needed to evaluate the safety and efficacy of antidepressants in PD and their effect on motor function.