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Journal of Psychopharmacology (Oxford,... Mar 2021Cariprazine is a dopamine D-preferring D/D receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is...
BACKGROUND
Cariprazine is a dopamine D-preferring D/D receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is clinically classified as a low-somnolence drug, to date no detailed polysomnographic study is available on its effect on sleep.
AIMS
This study examined the acute systemic effects of cariprazine on the rat sleep architecture and electroencephalography spectral power.
METHODS
Sprague Dawley rats were recorded during their normal sleep period for four hours, and their sleep stages were classified.
RESULTS
Cariprazine (0.3 mg/kg i.p.) reduced the time spent in rapid eye movement (REM) sleep and increased REM latency. This dose of cariprazine decreased the gamma (40-80 Hz) band frequency oscillations and increased the theta (4-9 Hz) and alpha (9-15 Hz) frequencies during the wake periods but not during slow-wave sleep. The 0.03 mg/kg dose of cariprazine only increased the alpha power during the wake periods, while the 0.003 mg/kg dose was without any effect.
CONCLUSION
Taken together, the present results suggest that the REM-suppressing effect of cariprazine may be related to its effectiveness in improving depressive symptoms, as various drugs with similar REM-reducing properties effectively treat the depressive state, whereas the gamma power-reducing effect of cariprazine may be indicative of its efficacy in schizophrenia or mania, as similar effects have been observed with other D and 5-HT receptor antagonist drugs. These data contribute to our understanding of the complex mechanism of action that may stand behind the clinical efficacy of cariprazine.
Topics: Animals; Antipsychotic Agents; Dopamine Agonists; Electroencephalography; Male; Piperazines; Rats; Rats, Sprague-Dawley; Sleep; Sleep, REM
PubMed: 33406962
DOI: 10.1177/0269881120981378 -
Pituitary Jun 2020Hyperprolactinemia is associated with suppression of the hypothalamic- pituitary-gonadal axis and consequent hypogonadism, manifesting loss of libido, infertility and... (Review)
Review
Hyperprolactinemia is associated with suppression of the hypothalamic- pituitary-gonadal axis and consequent hypogonadism, manifesting loss of libido, infertility and osteoporosis long-term in both male and female patients, with associated menstrual irregularities, amenorrhea and galactorrhea in women and erectile dysfunction in men. The primary goals of therapy in patients harboring prolactinoma are control of tumor size and normalization of serum PRL, with restoration of gonadal and sexual function and fertility. Clinical manifestations of hypogonadism have variable consequences depending on the age and sex of the patient and desire for fertility. Careful consideration of clinical consequences of hyperprolactinemia in relation to age and sex should help guide therapeutic decision making. Another important consideration in attaining our treatment goals in patients harboring microprolactinomas, is the observation that greater than 90% of microprolactinomas do not enlarge, when followed for 10 years. Treatment options for the management of microprolactinomas include observation alone, with monitoring of serum prolactin levels every 6-12 months, vs initiation of dopamine agonist therapy vs gonadal steroid hormone replacement (using the oral contraceptive or other combination estrogen and progesterone replacement regimens in females or testosterone replacement therapy in males). In the present review, current data related to clinical consequences of microprolactinomas and treatment outcomes at different stages in the lifespan are reviewed, with a suggested algorithm as to whether to treat or not, and an appropriate therapeutic regimen to institute.
Topics: Dopamine Agonists; Estrogens; Female; Humans; Hypogonadism; Male; Progesterone; Prolactinoma
PubMed: 32274622
DOI: 10.1007/s11102-020-01039-x -
Journal of Neural Transmission (Vienna,... Sep 2022The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan... (Review)
Review
The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus.
Topics: Amantadine; Dopamine; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Substance Withdrawal Syndrome
PubMed: 34324057
DOI: 10.1007/s00702-021-02389-x -
Expert Review of Neurotherapeutics Sep 2020Dopamine agonists have been widely used to treat patients with Parkinson's disease, but concerns related to their well-known side effects might prevent their use even... (Review)
Review
INTRODUCTION
Dopamine agonists have been widely used to treat patients with Parkinson's disease, but concerns related to their well-known side effects might prevent their use even when indicated. In this review, the authors describe for the first time the concept of 'Dopamine Agonist Phobia', a pharmacophobia that the authors believe might affect clinicians, and they provide evidence of the benefits of dopamine agonists, focusing on non-motor symptoms.
AREAS COVERED
The authors performed an extensive literature research, including studies exploring the use of dopamine agonists for the treatment of non-motor symptoms. The authors indicate the highest level of evidence in each section.
EXPERT OPINION
'Dopamine Agonist Phobia' may preclude valid therapeutic options in selected cases, specifically for the treatment of non-motor symptoms. Thus, the authors propose a personalized approach in Parkinson's disease treatment, and encourage a thoughtful use of dopamine agonists, rather than an overall nihilism.
Topics: Dopamine Agonists; Drug Prescriptions; Humans; Parkinson Disease; Practice Patterns, Physicians'
PubMed: 32755243
DOI: 10.1080/14737175.2020.1806059 -
The Cochrane Database of Systematic... May 2015Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development.
OBJECTIVES
To investigate the efficacy and acceptability of dopamine agonists alone or in combination with any psychosocial intervention for the treatment of of people who misuse cocaine.
SEARCH METHODS
We run the search on 12 January 2015. We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, CINAHL, PsycINFO, ICTRP, clinicaltrials.gov and screened reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing dopamine agonists alone or associated with psychosocial intervention with placebo, no treatment or other pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
Twenty four studies, including 2147 participants, met the inclusion criteria. Comparing any dopamine agonist versus placebo, we found no differences for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). This was also observed when single dopamine agonists were compared against placebo. Comparing amantadine versus antidepressants, we found low quality of evidence that antidepressants performed better for abstinence (RR 0.25, 95% CI 0.12 to 0.53) based on two studies with 44 participants. No differences were found for dropout or adverse events, for both moderate quality of evidence.The major flaws of the included studies concerned selection bias because most studies did not report information about sequence generation (80%) and allocation concealment methods (86%): half of the included studies were judged at unclear risk of performance bias and 62.5% at unclear risk of detection bias for what concerns subjective outcomes.
AUTHORS' CONCLUSIONS
Current evidence from RCTs does not support the use of dopamine agonists for treating cocaine misuse. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment. Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention, which was suggested by the previous Cochrane Review (Soares 2003), is not supported by the results of this Cochrane Review update.
Topics: Amantadine; Antidepressive Agents; Bromocriptine; Cocaine-Related Disorders; Depression; Dopamine Agonists; Humans; Levodopa; Randomized Controlled Trials as Topic; Selection Bias
PubMed: 26014366
DOI: 10.1002/14651858.CD003352.pub4 -
The Canadian Journal of Neurological... Sep 2023
Topics: Humans; Dopamine Agonists; Parkinson Disease; Suicide; Substance Withdrawal Syndrome; Disruptive, Impulse Control, and Conduct Disorders; Antiparkinson Agents
PubMed: 35801613
DOI: 10.1017/cjn.2022.272 -
Pituitary Feb 2020Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to... (Review)
Review
Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.
Topics: Bromocriptine; Dopamine Agonists; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactinoma
PubMed: 31792668
DOI: 10.1007/s11102-019-01010-5 -
BMC Research Notes Sep 2022There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function...
OBJECTIVE
There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function in patients with PD and matched controls. In PD subjects, we searched for factors contributing to endothelial dysfunction as well. Traditional vascular risk factors, PD characteristics, and PD medication were considered.
RESULTS
We prospectively enrolled 41 patients with PD and 41 controls matched for age, sex, body mass index, and vascular risk factors. Endothelial function (EF) was assessed using peripheral arterial tonometry (EndoPAT 2000 device) and expressed as reperfusion hyperemia index (RHI). Clinical characteristics including PD medication were recorded. RHI was non-significantly lower in the PD group than in controls (1.8 ± 0.5 vs. 1.9 ± 0.5, p = 0.478). In PD patients, in linear regression analysis, smoking (beta = -0.453, p = 0.008) and use of dopamine agonists (beta = -0.365, p = 0.030) were significant contributors in a model predicting RHI. Despite non-significant differences in endothelial dysfunction between PD patients and controls, our results suggest an association between smoking, dopamine agonists, and impaired EF in PD patients. The small sample size, as well as the absence of an extended search for traditional and non-traditional vascular risk factors, are the most important factors limiting the interpretation of the current results.
Topics: Dopamine Agonists; Endothelium, Vascular; Humans; Hyperemia; Parkinson Disease; Risk Factors
PubMed: 36064624
DOI: 10.1186/s13104-022-06176-z -
The Journal of Clinical Endocrinology... Mar 2020There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and...
CONTEXT
There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and predictive factors remain uncertain.
OBJECTIVE
To determine ICD prevalence and risk factors in DA-treated hyperprolactinemic patients compared to community controls.
DESIGN, SETTING AND PARTICIPANTS
Multicenter cross-sectional analysis of 113 patients and 99 healthy controls.
MAIN OUTCOME MEASURES
Participants completed a neuropsychological questionnaire consisting of the Depression Anxiety Stress Scale (DASS21), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP-S), Hypersexual Behavior Inventory (HBI), Hypersexual Behavior Consequences Scale and Social Desirability Response Set Scale. Demographic and clinical data were collated to determine ICD risk factors. Patients testing positive for an ICD were offered a semistructured psychological interview.
RESULTS
Patients were more likely than controls to test positive by QUIP-S for any ICD (61.1 vs 42.4%, P = .01), hypersexuality (22.1 vs 8.1%, P = .009), compulsive buying (15.9 vs 6.1%, P = .041) and punding (18.6 vs 6.1%, P = 0.012), and by HBI for hypersexuality (8.0 vs 0.0%, P = 0.004). Independent risk factors were male sex (odds ratio [OR] 13.85), eugonadism (OR 7.85), Hardy's tumor score and psychiatric comorbidity (OR 6.86) for hypersexuality, and age (OR 0.95) for compulsive buying. DASS21 subset scores were higher in patients vs controls and in patients with vs without different ICDs. Only 19/51 (37.3%) interviewed patients were aware of the relationship between DAs and ICDs before the study.
CONCLUSIONS
DA therapy poses a high, previously underestimated risk of ICDs, especially in the form of hypersexuality in eugonadal men.
Topics: Adult; Australia; Case-Control Studies; Cross-Sectional Studies; Disruptive, Impulse Control, and Conduct Disorders; Dopamine Agonists; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Male; Prevalence; Prognosis; Risk Factors; Surveys and Questionnaires
PubMed: 31580439
DOI: 10.1210/clinem/dgz076 -
Journal of Clinical Neuroscience :... Oct 2015The authors present an update on the various treatment modalities and discuss management strategies for prolactinomas. Prolactinomas are the most common type of... (Review)
Review
The authors present an update on the various treatment modalities and discuss management strategies for prolactinomas. Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. Dopamine agonist therapy is the first line of treatment for prolactinomas because of its effectiveness in normalizing serum prolactin levels and shrinking tumor size. Though withdrawal of dopamine agonist treatment is safe and may be implemented following certain recommendations, recurrence of disease after cessation of the drug occurs in a substantial proportion of patients. Concerns regarding the safety of dopamine agonists have been raised, but its safety profile remains high, allowing its use during pregnancy. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy.
Topics: Bromocriptine; Cabergoline; Disease Management; Dopamine Agonists; Drug Administration Schedule; Drug Resistance, Neoplasm; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neuroendoscopy; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactin; Prolactinoma; Radiosurgery; Sphenoid Sinus
PubMed: 26243714
DOI: 10.1016/j.jocn.2015.03.059