Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pramipexole is a clinically effective nonergot dopamine agonist. Pramipexole's receptor interactions differ from ergot agonists in several ways. First, it has high selectivity for interacting with dopamine D2 subfamily receptors (D2, D3, and D4 receptor subtypes) and has little interaction with adrenergic or serotonergic receptors. Second, within the D2 subfamily, it has preferential affinity for the D3 receptor subtype, which, according to preclinical studies, could contribute additional efficacy for treatment of both motor and psychiatric syndromes in Parkinson's disease. Third, it has full intrinsic activity at dopamine D2 subfamily receptors. In addition to pramipexole's unusual receptor profile, whole-animal and cell culture studies suggest that pramipexole might provide neuroprotective effects through depression of dopamine metabolism, antioxidant effects, and stimulation of trophic activity. Pramipexole's demonstrated clinical efficacy for successful treatment in early disease for several years in the absence of L-dopa and as adjunctive therapy with L-dopa in late disease suggests a potential new paradigm for treatment of Parkinson's disease whereby new patients are initiated with pramipexole therapy and L-dopa is added only as necessary.
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PMID:Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. 961 5

Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20 mg and placebo in a randomized, double-blind, parallel-group study. After a 1 week placebo run-in period, patients were treated for 8 weeks, had a post-study follow-up (week 9), and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinician's Global Impressions-Severity of Illness scale (CGI-SI). All patients who received one dose of study medication were included in the observed-case analysis (no missing data were replaced). Results indicated that by endpoint (week 8), patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D, MADRS, and CGI-SI. Significant improvement in this dose group was seen at other timepoints as well. The most obvious improvement was seen in the pramipexole 5.0 mg group, although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study. Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study. Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day.
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PMID:Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. 1081 30

Parkinson's disease (PD) is a common neurodegenerative disorder characterised by selective loss of dopaminergic neurones in the substantia nigra and resulting in progressive disability. Therapy has focused on replacing depleted dopamine (DA) via supplementation with levodopa or DA agonists. Pramipexole (Mirapex), Pharmacia Corp.) has recently been approved for the treatment of PD. Evidence from preclinical studies and clinical trials have proven the effectiveness of this agent in ameliorating the symptoms of PD. There is also non-human evidence that pramipexole may be neuroprotective and could therefore possibly slow disease progression; however, this has yet to be proven in humans. The use of pramipexole may be limited by its side effect profile compared to standard therapies and its relatively higher cost compared to levodopa. Despite these concerns, pramipexole does have a role in the treatment of PD in all stages of the illness and may arguably be the treatment of choice in early disease. In addition to its use in PD, pramipexole has shown some utility in the treatment of restless legs syndrome (RLS), depression and schizophrenia.
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PMID:A review of pramipexole and its clinical utility in Parkinson's disease. 1182 33

In a single-blind, placebo-controlled crossover trial, the acute efficacy of the dopamine agonist pramipexole was investigated in 11 restless legs syndrome (RLS) patients by sleep laboratory methods, with a clinical follow-up for 4 weeks. In 3 nights (pre-treatment, placebo and drug night), objective sleep quality was determined by polysomnography (PSG), subjective sleep and awakening quality by rating scales, objective awakening quality by psychometry. Clinical follow-up consisted of completion of the International RLS Study Group (IRLSSG) Scale, Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Concerning acute effects, an omnibus significance test for PSG variables demonstrated a global difference between placebo and pramipexole, but none between pre-treatment and placebo. Pramipexole 0.27 mg significantly decreased the target variable periodic leg movements (PLM)/h of sleep as well as all other RLS/PLM variables and improved objective sleep efficiency and subjective sleep quality as compared with placebo. In sleep architecture, sleep stages S1 and S2 and stage shifts increased, while slow-wave sleep and SREM decreased. After 4 weeks of therapy, the total scores of the IRLSSG questionnaire, sleep quality and daytime sleepiness, depression and quality of life also improved. Thus, acute pramipexole markedly reduced PLM measures and slightly improved objective and subjective sleep quality. Follow-up ratings showed a moderate improvement of RLS and sleep quality, and to a lesser extent of daytime sleepiness, depression and quality of life. The psychopathological findings as well as acute sleep architecture changes are reminiscent of those seen after activating antidepressants.
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PMID:Acute placebo-controlled sleep laboratory studies and clinical follow-up with pramipexole in restless legs syndrome. 1224 80

Pramipexole is a novel, internationally available selective nonergot D2 dopamine agonist. The effectiveness, tolerability, and safety of pramipexole have been extensively proven in controlled trials in patients in the early and advanced stage of Parkinson's disease as monotherapy and in combination with L dopa. These trials indicated specific activity against tremor, anhedonia, and depression. Therefore, the present prospective, multicenter postmarketing surveillance study evaluated for the first time to what extent the results from the controlled pramipexole trials could be replicated under routine conditions in neurological practice and clinics. Modern scales were applied for the assessment of tremor and mood, i.e., the Short Parkinson's Evaluation Scale (SPES), the Tremor Impact Scale (TIS), and the German version of the Snaith-Hamilton Pleasure Scale (SHAPS-D). In 298 German Centers, 657 Parkinson's patients (365 men, 292 women) in advanced disease stages were treated with pramipexole in combination with levodopa. The average ages (+/- SD) were 67 (+/- 8.9) years for men and 69 (+/- 9.4) years for females. Motor functioning, especially tremor, motor complications, depression, and activities of daily living improved highly significantly (P < 0.0005), including self-rating by the patients. The dosage of levodopa could be reduced on average by 8% (P < 0.0001). This might contribute to a slowing of the disease progression in the long run. Dropouts due to side effects were observed only in 3.5% of the patients. Using new assessment scales suitable for routine application allowed confirmation of the results from controlled clinical trials with regard to tremor, anhedonia, and depression. The average daily dosage of pramipexole prescribed was 1.05 mg and thus was definitely lower than the average daily dosages of 2.35-2.66 mg used in controlled trials. This signifies that the option to adjust dosage according to effectiveness and tolerability under routine conditions yields a considerably lower incidence of adverse effects.
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PMID:[Pramipexole in Parkinson disease. Results of a treatment observation]. 1224 61

We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score= <2 at LIFE for at least 8 weeks) and recurrence (after remission score > =3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 had bipolar depression (16 women; mean age=52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects had at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 28 weeks. Mean baseline MADRS and CGI-S scores were 33.7+/-8.4 (sd) and 4.6+/-0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression.
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PMID:Pramipexole in treatment-resistant depression: an extended follow-up. 1554 89

We describe a retrospective case series of three patients, two with bipolar depression and one with unipolar depression. Pramipexole is a Food and Drug Administration-approved antiparkinsonian agent, which, when used to augment antidepressants, would be considered an off-label use and should be discussed with the patient. These patients had robust responses to pramipexole augmentation of their treatment regimen. All three patients had been taking an atypical antipsychotic. The depressive symptoms were evaluated using the Hamilton Rating Scale for Depression.
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PMID:Pramipexole: augmentation in the treatment of depressive symptoms. 1657 73

Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.
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PMID:Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease. 1681 8

Body weight changes occur during the clinical course of Parkinson's disease (PD) and with surgical treatment, but the effect of dopaminergic treatment on weight is unknown. Body mass index (BMI), Hamilton depression scale score (HDS), and Unified Parkinson's Disease Rating Scale III (UPRS-III) were measured before and 3 months after starting pramipexole in 28 PD patients. Pramipexole produced a significant weight increase, as well as motor and mood improvement (P <0.001). HDS and BMI changes were mildly related (P = 0.05). A direct effect of pramipexole on limbic D(3) receptors involved in the control of feeding may be responsible for weight gain in PD.
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PMID:Increase in body weight after pramipexole treatment in Parkinson's disease. 1697 76

We present a first case of Parkinson's disease with neuroleptic malignant syndrome by Paroxetine, one of the selective serotonin reuptake inhibitor (SSRI). The patient was a 73-year-old woman who had been diagnosed as Parkinson's disease for one and half year. The severity of her disease was categorized as Hoehn & Yahr 2nd degree and she had taken 0.25 mg/day of Pramipexole. Four days after the addition of 10 mg/day of Paroxetine for the treatment of her depression, she developed consciousness disturbance, severe muscular rigidity, tremor, fever, hyperhidrosis, incontinence and elevated serum creatine kinase level. According to diagnostic criteria, she was diagnosed as neuroleptic malignant syndrome probably induced by Paroxetine. Her clinical symptoms and laboratory data were improved seven days after intravenous drip infusion. We should recognize that SSRI could induce neuroleptic malignant syndrome in patients with Parkinson's disease.
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PMID:[A case of Parkinson's disease with neuroleptic malignant syndrome induced by paroxetine]. 1715 40


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