Beneficial effect of pramipexole for motor function and depression in Parkinson’s disease

We examined whether pramipexole (PPX) can influence depressive scale in normal and mild depressive parkinsonian patients. In an open study of PPX as an add-on to L-dopa therapy or single administration, 36 nondemented outpatients with Parkinson’s disease (PD) were entered first. All were in the stage II or III of Hoehn and Yahr scale (H&Y). PPX were started at 0.125 mg/day and daily doses were increased to 1.5 mg/day. At 3 months after PPX treatment, patients were re-evaluated. Hamilton Depression Rating Scale (HAM-D), Unified Parkinson’s Disease Rating Scale III, H&Y stage, and freezing of gait questionnaire were compared in patients before and after PPX treatment. These scores were significantly improved after PPX administration. There were no correlations between HAM-D and those motor functions. We suggest that PPX treatment has antidepressant effects in depressive PD patients and also ameliorates HAM-D score in nondepressive PD patients in addition to motor function.     

Factors associated with depression in Parkinson’s disease: a cross-sectional study in a Polish population

OBJECTIVE: The aim of this study was to assess the prevalence and factors influencing depression in PD patients in a cross-sectional outpatient clinic - based Polish patients sample. MATERIALS AND METHODS: One hundred consecutive PD patients were included in this study; 35 of them fulfilled DSM-IV criteria for Major Depression and its severity was assessed with Montgomery-Asberg Depression Rating Scale (MADRS). A structured interview and a neurological examination, including Hoehn and Yahr scale (H-Y), Schwab-England disability scale, II, III, IV parts of Unified Parkinson's Disease Rating Scale (UPDRS), and Mini-Mental State Examination (MMSE) were performed. The parameters obtained were analysed between the depressed and non-depressed PD patients. RESULTS: The prevalence of depression in PD in Polish population was established at the level of 35%. PD patients with depression scored significantly higher in all UPDRS scales (except for the subscale of clinical fluctuation) and in H-Y scale. PD with depression was also associated with longer PD duration, higher doses of L-dopa equivalents, patients' age, general impairment of daily living in Schwab and England disability scale, lower MMSE and higher clinical fluctuations. However, those six differences were insignificant. CONCLUSIONS: Depression prevalence rate among PD patients in Polish population is slightly lower than in most of other published studies. This may result from strict selection criteria, use of specific outcome measures and restricted criteria for depression that were applied.     

Depression rating scales in Parkinson's disease: critique and recommendations.

Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.     

Depression and care-dependency in Parkinson's disease: results from a nationwide study of 1449 outpatients

Parkinson's disease (PD) is frequently compounded by neuropsychiatric complications, increasing disability. The combined effect of motor and mental status on care-dependency in PD outpatients is not well characterized. We conducted a cross-sectional study of 1449 PD outpatients. The assessment comprised the Montgomery-Asberg Depression Rating Scale (MADRS) and the diagnostic criteria for dementia. PD severity and treatment complications were rated using Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale (UPDRS) IV. The acknowledged level of care-dependency was documented. Care-dependency was present in 18.3% of all patients. A total of 13.9% had dementia, 18.8% had depression, and 14.3% had both. Regression analyses revealed increasing effects of age, PD duration, and PD severity on care-dependency in all three mental-disorder subgroups with the strongest effects in patients with depression only. Depressed patients with antidepressive treatment still had significantly higher PD severity, higher MADRS and UPDRS-IV scores but were not more likely to be care-dependent than non-depressed patients. Older age, longer duration and increased severity of PD contribute to care-dependency in patients with untreated depression. Treatment of depression is associated with lower rates of care-dependency.     

影响帕金森病患者生活质量的因素

目的探讨影响帕金森病(PD)患者生活质量的因素。方法采用PD生活质量问卷(PDQL)、PD统一评定量表(UPDRS)、Hoehn-Yahr分期、Schwab-England残疾量表、汉密顿抑郁量表(HAMD)对71例PD患者的生活质量、疾病严重程度、日常生活能力、运动反应、精神状态及治疗并发症等指标进行评估,结合患者的年龄、性别、起病情况、吸烟、左旋多巴剂量、症状波动等因素评价其对生活质量的影响。结果一元相关分析显示:病程越长、治疗时间越久、左旋多巴剂量越大、UPDRS各项评分、Hoehn-Yahr分期越高,以及有抑郁或症状波动的PD患者生活质量越差(P<0.05～0.01)。逐步回归分析显示:影响PD患者生活质量的主要因素是患者的情感功能,其次是疾病的严重程度。结论情感功能是影响PD患者生活质量最重要的因素。     

Greater depression severity associated with less improvement in depression-associated cognitive deficits in older subjects.

OBJECTIVES: Elderly depressed patients often exhibit cognitive deficits, which may improve with drug therapy. The authors investigated the relationship of baseline depression severity and cognitive improvement with antidepressant treatment in depressed patients with mild cognitive impairment. METHODS: Mini-Mental State Exam (MMSE) and Montgomery-Asberg Depression Rating Scale (MADRS) scores were measured in 52 depressed geriatric patients without dementia at baseline, 6, and 12 months, during an intent-to-treat period. A repeated-measures regression model tested the effect of MADRS score on MMSE. RESULTS: MMSE changes were significant and linear over time, with an average increase of 0.72 in the MMSE per 6-month interval. The final model showed that for every point increase in baseline MADRS, the average 6-month increase in MMSE decreased by 0.12. Repeated MADRS measurements did not significantly alter its predictive value. CONCLUSION: Greater baseline depression severity in older subjects with mild cognitive deficits is associated with less improvement in those deficits even with successful antidepressant therapy.     

丘脑底核脑深部电刺激治疗帕金森病合并抑郁障碍的长期疗效

目的研究丘脑底核（STN）脑深部电刺激（DBS）治疗帕金森病（PD）合并抑郁障碍的长期疗效并探讨其神经机制。方法对15例合并抑郁障碍的PD患者实施STN脑深部电极植入，术后3个月、6个月和12个月进行随访和临床评价。结果术后运动功能症状如肢体僵硬、震颤、运动迟缓和姿势平衡障碍改善良好，停药后PD分级量表运动评分显著下降（P〈0．01）。术后抑郁障碍症状如焦虑、绝望和激越症状改善良好，停药后汉密尔顿抑郁量表评分显著下降（P〈0．05）。结论STN-DBS能显著改善PD的抑郁障碍症状，STN在PD抑郁障碍神经机制中起重要作用。     

Improvement in depression associated with partial epilepsy in patients treated with lamotrigine

Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Previous studies indicate that lamotrigine may have antidepressant properties. Thirteen adults with uncontrolled partial seizures and concomitant depression were evaluated using measures of depression [Montgomery and Asberg Depression Rating Scale (MADRS) and the MMPI Depression Scale] and anxiety [Spielberger's State-Trait Anxiety Inventory (STAI)] to test the effects of lamotrigine on mood. Evaluations after 5 weeks and again after 3 months of lamotrigine treatment demonstrated significant improvement in depression and anxiety. Mean MADRS overall scores were significantly lower than pretreatment baseline at the 5-week and 3-month evaluations. The mean MMPI Depression score was significantly lower than baseline at the 3-month evaluation. State anxiety scores were significantly reduced from baseline after 5 weeks, but not at 3 months, whereas Trait anxiety scores were reduced from baseline at the 5-week and 3-month evaluations.     

A 12-week double-blind multi-centre study of paroxetine and imipramine in hospitalized depressed patients

Fifty-seven inpatients with major depression (DSM-III-R) entered a 12-week study comparing paroxetine and imipramine. Trends (not reaching statistical significance) in favour of paroxetine were seen on the Hamilton Depression Rating Scale (HDRS) and the Montgomery-Åsberg Depression Rating Scale (MADRS). The UKU Side Effect Rating Scale showed a significant difference in favour of paroxetine on reduced salivation. Global evaluation of side effect symptoms showed that significantly more paroxetine patients had no side effects, both in the investigators’ and the patients’ opinion. These results are in line with previous findings of paroxetine being an effective and well tolerated antidepressant.     

Depressive symptoms in Parkinson's disease

ObjectiveWe aimed to investigate the relationship between the presence and severity of depression and the degree of motor and functional disability in Parkinson's disease (PD).MethodsOne hundred twenty-two outpatients with PD were enrolled in a neurology department: 65 satisfied the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for major depression, and 57 did not (PD-C). Depressive symptoms were assessed by means of the Hamilton Rating Scale for Depression (HRSD), and the PD severity was assessed according to the Hoehn and Yahr System. Activities of daily living and motor symptoms were measured by the Unified PD Rating Scale (UPDRS), parts II and III.ResultsTwenty-nine patients had a mild depression (HRSD total score ranging between 8 and 17), 30 had a moderate depression (HRSD total score ranging between 18 and 24), and 6 had a severe depression (HRSD total score, ≥25). By comparing the 3 groups of patients, it emerged that those with a severe depression showed significantly higher scores at the UPDRS II, UPDRS III, and HY scales than did PD-C or patients with a mild depression. Moreover, patients with a moderate depression scored significantly higher on the UPDRS II, UPDRS III, and HY scales than did PD-C or those with a mild depression.ConclusionsOur findings suggest that depression and motor symptoms/well-being are highly intertwined in patients with PD.     

The relationship of pain and health-related quality of life in Korean patients with Parkinson's disease

Background – Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder. Increasing attention has been focused on the pain and health‐related quality of life (HrQOL) in patients with PD. Objective – To evaluate the relationship between pain and the HrQOL in patients with PD. Methods – Eighty‐two patients with PD were included and classified into two groups according to the presence of pain. The Hoehn and Yahr scale, the Unified Parkinson’s Disease Rating Scale (UPDRS), the Modified Somatic Perception Questionnaire (MSPQ), the Zung Depression Inventory – Self‐rating Depression Scale (SDS), the Visual Analogue Scale and the Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36) were administered. The factors influencing the pain, HrQOL and parkinsonian manifestations were evaluated. Results – The PD with pain group had higher UPDRS part III scores, lower SF‐36 scores, higher SDS scores and higher MSPQ scores than the PD without pain group. The presence of pain, high Hoehn and Yahr stage, advanced age and somatic perception were the factors that had a negative effect on the physical component of the HrQOL. Depression and somatic perception were the most important predictive factors for the mental component of the HrQOL. Depression and poor parkinsonian motor abilities were the leading factors contributing to pain. Conclusion – Pain and depression were major detrimental factors affecting the physical and mental aspects of the HrQOL respectively. Therefore, the treatment of pain and depression can be important to improve the HrQOL.     

Effect of levetiracetam on depression and anxiety in adult epileptic patients

BACKGROUND: Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Some studies indicate that levetiracetam (LEV) may have mood stabilizing properties. METHODS: Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV. Patients were evaluated for depression and anxiety with several psychometric measures, including: Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-rating Scale for Depression (Z-SDS), Hamilton Anxiety Rating Scale (HARS), Zung Self-rating Scale for Anxiety (Z-SAS). RESULTS: Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety. CONCLUSIONS: This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures. However, the sample of patients is limited and the possibility of a placebo effect cannot be excluded. These findings must be considered preliminary and should be replicated under placebo-controlled conditions.     

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.     

Characteristics of depression in Parkinson's disease: evaluating with Zung's Self-Rating Depression Scale

The purpose of the study was to elucidate characteristics of depression in Parkinson's disease (PD). Fifty-eight PD patients were evaluated with Zung's Self-Rating Depression Scale (SDS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Scores for "suicidal ideation" on the SDS correlated with posture and gait disturbances on the UPDRS. Twenty-six patients with spinocerebellar degeneration (SCD) were also evaluated with the SDS. SDS scores for "indecisiveness" and "constipation" were significantly higher in PD patients than SCD patients. Our results suggest that depression is common in disabled persons but PD patients might have a characteristic clinical presentation.     

Social support plays a role in depression in Parkinson's disease: a cross-section study in a Chinese cohort

To investigate the association between social support and depression in Parkinson's disease (PD), 121 PD patients were enrolled in our study. Interview of questionnaires and neurological examinations, including Hamilton Depression Rating Scale, Chinese Social Support Rating Scale (SSRS), Hoehn and Yahr Stage, Schwab and England Scale (SE) and unified PD Rating Scale (UPDRS) were performed. Increased level of UPDRS and lowered social support were associated with depression in PD patients. Stepwise regression analysis showed that objective social support, UPDRS part 1 and duration of disease manifested significant correlation to patients' depression degree. Therefore, social support plays an important role in depression in PD.     

A double-blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice.

OBJECTIVE: This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice. METHODS: In this double-blind, multicentre study conducted in the general practice, patients with depression (Montgomery Asberg Depression Rating Scale [MADRS] score > or = 20) who were regarded as requiring antidepressant therapy were randomly assigned to receive paroxetine (20 mg, n = 184) or amitriptyline (50-100 mg, n = 191) once daily for 9 weeks. RESULTS: More patients completed treatment with paroxetine than with amitriptyline (71.1% vs 56.1%, p = 0.009). Depression rating scores (MADRS and Clinical Global Impression [CGI]) were improved with both agents, but at week 9, paroxetine achieved more favourable scores compared with amitriptyline on MADRS (p=0.019), CGI severity of depression (p=0.044), and CGI efficacy index (p = 0.038). CONCLUSIONS: Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline.     

Pre-existing antidepressant medication and the outcome of group cognitive-behavioural therapy

OBJECTIVE: This study aimed to investigate the impact of pre-existing medication on the outcome of group cognitive-behavioural therapy (CBT) in the treatment of patients with depression. METHOD: Of the 71 patients diagnosed with major depression who participated in group CBT, 25 were on medication (CBT-M) and 46 were unmedicated (CBT). The patients received 12 sessions of group CBT over a 3-month period. The dependent measures used were the Beck Depression Inventory, Zung Self-Rating Depression Scale, Automatic Thoughts Questionnaire, Hopelessness Scale, Dysfunctional Attitude Scale, Daily Activity Rating Scale and Daily Mood Rating Scale. RESULTS: Both the CBT and CBT-M groups showed statistically significant improvement in depression scores and cognitive process measures. However, the rate of improvement for both groups on these measures did not differ. CONCLUSION: The study indicated that pre-existing antidepressant medication did not enhance or detract from the positive treatment outcome of depressed patients receiving a group CBT treatment.     

An examination of the sensitivity of the six-item Hamilton Rating Scale for Depression in a sample of patients suffering from major depressive disorder

OBJECTIVES: To compare the sensitivity of the 6-item Hamilton Rating Scale for Depression (HRSD6) with the more widely used 17-item Hamilton Rating Scale for Depression (HRSD17) in patients suffering from major depressive disorder, with or without melancholia and/or dysthymic disorder. A secondary objective was to compare the sensitivity of the HRSD6 to the Montgomery-Asberg Depression Rating Scale (MADRS). DESIGN: Retrospective analysis of 4 clinical trials that tested antidepressant therapies. SETTING: Outpatient treatment in a major psychiatric hospital. PARTICIPANTS: One hundred and forty-three male and female outpatients meeting the criteria of the DSM-III-R or DSM-IV for major depressive disorder. OUTCOME MEASURES: HRSD17, HRSD6 and MADRS. RESULTS: The HRSD6 correlated strongly with the HRSD17, both at baseline and termination of treatment, and for the subgroups of double depression and melancholia. The HRSD6 was also correlated significantly with the MADRS at both measurement times, and for the subgroups. Paired t-tests with the HRSD6, HRSD17 and MADRS demonstrated equal sensitivity to change over the course of treatment, both in the full sample and in the dysthymic and melancholic subgroups. CONCLUSIONS: The HRSD6 appears to be as sensitive to change over treatment as the HRSD17 and the MADRS. A shorter, less time-consuming measure of depression may have utility in clinical practice and research.     

The assessment of depression in Parkinson's disease

Background:  Motor symptoms form the hallmark of Parkinson's Disease (PD), although features like depression are often present. Depression rating scales [e.g. Montgomery-Åsberg Depression Rating Scale (MADRS)] used in PD measure affective, cognitive and somatic symptoms. An important clinical question is which items of the MADRS are likely to be influenced by PD symptoms.
Methods:  Depression was assessed in 43 PD patients who scored below the cut-off of the MADRS and who differed widely in motor severity.
Results:  Parkinson's Disease patients scored relatively highest on Concentration difficulties, Reduced sleep and Inner tension. Reduced sleep, Lassitude and Suicidal thoughts were associated with motor severity and specifically with Bradykinesia, Rigidity and Axial impairment, however not with Tremor.
To avoid a possible influence on our results of coincidentally included PD patients with a depression, all associations between somatic MADRS items and motor severity were corrected for the influence of affective symptoms of depression. All associations remained significant.
Discussion:  In conclusion, the items Reduced sleep and Lassitude of the MADRS are likely to be influenced by motor symptoms. The high score on Concentration difficulties is suggested to be a reflection of cognitive dysfunction in PD. Thus, when assessing depression in PD, using a depression rating scale like the MADRS, adjusted cut-off scores are required.     

The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized,double‐blind,placebo‐controlled study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society