Anhedonia: (lack of pleasure in life).

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Adjunctive dopamine agonists in treatment-resistant
bipolar II depression: an open case series
by
Perugi G, Toni C, Ruffolo G, Frare F, Akiskal H.
Department of Psychiatry,
University of Pisa, Italy.
[email protected]
Pharmacopsychiatry 2001 Jul; 34(4):137-41

ABSTRACT
OBJECTIVE: Previous studies and case observations have suggested that dopamine agonists (DAAs) such as pramipexole (PPX) and ropinirole (RPN) might be effective for major depression, but their adjunctive use in treatment-resistant bipolar II depression has not yet been specifically addressed. METHOD: A chart review was conducted on 18 patients with a DSM-III-R bipolar NOS (Bipolar II) major depressive episode who were admitted to the day-hospital of the Department of Psychiatry at the University of Pisa. DAAs were added to ongoing treatments with conventional antidepressants and mood stabilizers to which patients had no responded after a period of at least 8 weeks. Clinical state and adverse effects were assessed at each visit. Final improvement in CGI scores of 1 or 2 were considered as responders. RESULTS: Mean DAA trial duration was 17.6 (sd = 7.8, range 4-34) weeks, with a mean final dose of 1.23+/-0.32 mg/day (range, 0.75-1.50mg/day) for PPX, and 2.97+/-0.99mg/day (range, 1.50-5.00mg/day) for RPN. DAAs were well tolerated and did not show any negative interaction with concomitant psychotropic medications. Only one patient became worse (final CGI = 5), and had to interrupt PPX due to nausea, increased agitation and irritability. Eight patients (44.4%) were considered responders (4 with PPX and 4 with RPN): 5 showed marked improvement (CGI = 1), and 3 showed moderate improvement (CGI = 2); another 5 (27.8%) manifested a transient response not sustained up to the end. The initial and final scores of CGI severity scale for all patients (responders and non-responders combined) were, respectively, 5.33+/-0.7 and 3.94+/-1.3 (mean +/- S.D). The mean change according to the CCI severity scale was statistically significant (t=4.74. p < 0.0002). CONCLUSION: From the results, PPX and RPN appear to be well tolerated and potentially useful in the adjunctive treatment of drug-resistant bipolar II depression.

Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice
by
Lehr E.
Department of Pulmonary Research,
Boehringer Ingelheim Pharma KG,
55216 Ingelheim am Rhein, Germany.
[email protected]
Psychopharmacology (Berl) 2002 Oct;163(3-4):495-500

ABSTRACT
RATIONALE: Pramipexole is a dopamine agonist which binds selectively to dopamine D(3) and D(2) receptors. There is evidence that, in addition to its beneficial effects in parkinsonism, this compound may also be of value in addressing symptomatology associated with depressive diseases. OBJECTIVES: The present study was aimed at investigating behavioral effects of pramipexole that may indicate possible antidepressant properties. METHODS: We measured how different doses of pramipexole influence nocturnal locomotion and operant responding after prolonged conditioning of a schedule of FI 2 min (FI2) in female NMRI mice. RESULTS: The present data indicate that active doses of pramipexole inhibit nocturnal locomotion during the first hour after administration and later elevate activity in mice. After prolonged FI conditioning some of the mice changed to a pattern of lowered responding prior to reinforcement ("low temporal control") whereas others maintained the typical high increase of responding prior to reinforcement ("high temporal control"). Additionally, low oral doses of pramipexole increase operant behavior in "low temporal control" mice prior to reinforcement leaving the pattern of operant responding of "high temporal control" mice unchanged. CONCLUSIONS: Based on other preclinical data and initial clinical results, we speculate that these effects may reflect anti-anhedonic/antidepressive properties of pramipexole.

Synergistic effect of pramipexole and sertraline
in the forced swimming test
by
Maj J, Rogoz Z.
Department of Pharmacology,
Institute of Pharmacology,
Polish Academy of Sciences, Krakow.
Pol J Pharmacol 1999 Nov-Dec;51(6):471-5

ABSTRACT
The authors studied the effect of sertraline, one of selective serotonin reuptake inhibitors (SSRIs), and pramipexole, administered jointly, to male Wistar rats in the forced swimming test. Both those drugs were injected three times (24, 5 and 1 h before the test): sertraline at doses of 5 and 10 mg/kg ip, pramipexole at doses of 0.05, 0.1 and 0.3 mg/kg sc. Sertraline given separately was inactive in the test used. Pramipexole reduced the immobility time only at a dose of 0.3 mg/kg. Joint administation of both those drugs distinctly shorted the immobility time, that effect.being particularly strong at pramipexole, 0.3 mg/kg, and sertraline, 5 or 10 mg/kg. The obtained results indicate that sertraline--like the previously tested citalopram and fluoxetine--shows a synergistic effect when given with pramipexole in the forced swimming test.

Pramipexole in treatment-resistant depression:
a 16-week naturalistic study
by
Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR,
Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.
Department of Psychiatry, Neurobiology,
Pharmacology and Biotechnologies, University of Pisa, Italy.
[email protected]
Bipolar Disord 2002 Oct;4(5):307-14

ABSTRACT
OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.

After treatment with pramipexole, 13 of the 22 patients experienced complete or impressive alleviation of their depressive state; six were taking pramipexole alone, and seven had pramipexole added to their current antidepressant regimen, which had previously been ineffective.

Effectiveness of Pramipexole for Treatment-Resistant Depression

This study is currently recruiting patients.
Verified by National Institute of Mental Health (NIMH) June 2006Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00231959



Purpose
This study will evaluate the effectiveness of pramipexole (Mirapex) in managing treatment-resistant depression.Condition Intervention Phase
Depression Drug: Pramipexole (Mirapex) Phase IV


MedlinePlus related topics: Depression

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Double-Blind Placebo-Controlled Trial of Adjunctive Pramipexole, a Dopamine Receptor Agonist, for Treatment Resistant Major Depressive Episodes
Further study details as provided by National Institute of Mental Health (NIMH):
Primary Outcome Measures:
Score on the Montgomery-Asberg Depression Rating Scale; measured at Week 8 and monthly for the duration of the 6-month optional continuation phase for responders
Score on the CGI scale; measured at Week 8 and monthly for the duration of the 6-month optional continuation phase for responders

Total Enrollment: 80

Study start: September 2003

Depression is a serious medical illness, for which various types of treatment have been developed. Both medications and therapies have proven effective in treating depression. However, some people with depression do not benefit from these treatments. New medications are needed for treating depression in those who have not responded to commonly used antidepressants. Pramipexole (Mirapex) is most often used for the treatment of Parkinson’s disease, but has been reported to have antidepressant effects as well. This study will evaluate the effectiveness of pramipexole in treating depression in individuals that have not responded to other medications.

Participants in this double blind study will be randomly assigned to receive either pramipexole or placebo, in addition to their current medications, for 8 weeks. Treatment response will be assessed at the end of this phase by measuring symptoms of depression. At this time, those individuals who have responded to treatment will have the option to continue in a 6-month follow-up study. Participants will be seen monthly throughout the 6 months to assess treatment response. Participants who do not exhibit a response to treatment will be tapered off the medication. All participants will receive 3 months of follow-up care, regardless of their response to the medication.

Eligibility
Ages Eligible for Study: 18 Years - 75 Years, Genders Eligible for Study: Both
Criteria

Inclusion Criteria:
Meets diagnostic criteria for major depressive disorder
Meets criteria for current major depressive episode
Score of at least 18 on the Montgomery-Asberg Depression Rating Scale (MADRS) at the baseline visit
Currently being treated with antidepressant monotherapy at an adequate dose for 6 weeks or willing to enter open lead-in treatment
Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:
Pregnant
At risk for suicide or homicide
Unstable medical illness (e.g., cardiovascular, liver, kidney, respiratory, endocrine, or neurologic disease, including uncontrolled seizure disorder)
History of a substance use disorder within 6 months of study enrollment
History of or current psychotic features
Currently being treated with typical or atypical antipsychotic medications
Currently being treated with a medication known to significantly decrease pramipexole clearance (e.g., cimetidine, ranitidine, diltazem, verapamil, quinine or triamterene)
Clinical or laboratory evidence of untreated hypothyroidism
History of a 2-week or longer course of pramipexole
Intolerance of pramipexole at any dose
Any investigational psychotropic drug use within the last three months
Level 3 or greater antidepressant resistance as assessed by the ATHF
Three or more episodes of self-harm in the year prior to study enrollment
Documented history of poor treatment adherence or frequently missed appointments
Parkinson's disease

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00231959

Deborah Shear 617-726-0517 [email protected]

United States, Massachusetts
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, 02114, United States; Recruiting
Deborah Shear 617-726-0517 [email protected]
Roy Perlis, MD 617-726-7426 [email protected]
Roy Perlis, MD, Principal Investigator

Study chairs or principal investigators

Roy Perlis, MD, Principal Investigator, Massachusetts General Hospital

Emotional blunting is not control; we are supposed to have emotions.