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Limitations include the single-subject case study. However, as many individuals with PG may have co-morbid AD, future studies of disulfiram in this population warrant consideration. Additional case studies report on disulfiram in treating PG. The first patient was a year-old male with no previous psychiatric treatment history and no co-occurring disorders.
He was started on outpatient cognitive behavioral therapy and offered pharmacological treatment in conjunction. He did not want to be treated with SSRIs so he chose to take disulfiram. He also reported adverse effects of sedation and an increase in hours slept per day. Seventeen days into his treatment he relapsed and discontinued the medication himself for a one-week period, after which he began to take the medication again.
He continued with the medication but kept experiencing sedation. The second patient was a year-old male. He had received previous psychiatric treatment for depressive episodes at ages 33 and In addition, he was able to achieve abstinence from his gambling, during his last depressive episode, for one year.
He had additional periods of abstinence from counseling visits of up to four weeks, but due to continuous relapses, he presented for additional treatment options. His therapy initially involved cognitive behavioral therapy and due to his lack of responses to previous treatments with citalopram and venlafaxine he was offered disulfiram.
The patient tolerated the medication well in the beginning, but there was no significant impact on his gambling. After just a short period of being on the medication 23 days , the patient developed psychotic symptoms necessitating admission to an inpatient unit.
Disulfiram was discontinued and his symptoms remitted almost completely within three days. In both case reports, the dose of disulfiram was much smaller than with other treatment studies involving cocaine or alcohol. However, due to the side effects both patients exhibited, higher doses were not an option. As the only studies to date are case studies, a larger clinical trial is needed to better determine the efficacy and tolerability of disulfiram in treating PG, particularly in individuals with co-occurring AD.
It is thought to reduce glutamate excitability and has been used primarily in treating cognitive decline in patients with Alzheimer's disease. It has shown efficacy in treating alcoholism, and thus may have efficacy in treating PG. In the only study to date to examine the efficacy and tolerability of memantine in treating PG, Grant et al.
Twenty subjects completed the entire study this higher than normal retention rate was noted by the authors. In addition to improvement on gambling measures, the authors noted an increase in cognitive flexibility. Side effects were minimal and included headaches, dizziness, and lethargy, all of which were of mild to moderate intensity and resolved without additional effects.
Limitations of this study include the open-label nature of the study, that weekly visits with a clinician may have introduced bias, the small sample size, and the short duration of the trial. In a case study out of Brazil, Nicolato et al. Her affective state improved but there was no concurrent improvement in her gambling behavior. After 2 months of combined treatment, her gambling behavior remitted.
Long-term follow-up showed continued abstinence. In the only report of acamprosate in the treatment of PG, Raj described a case study of a year-old woman with a long history of depression who presented to his clinic in May for treatment of depressive symptoms She was determined to have AD and PG, although the patient had not been seeking treatment for either condition.
She was started on venlafaxine for depression given a prior response to the medication. She was not seen again until September She presented for a follow-up visit just prior to entering an alcohol treatment program, stating she could no longer control her drinking or gambling.
At this time, she was only looking for treatment for her AD. By January of , the patient was reporting partial remission of her AD, but full remission of her PG. At one point her acamprosate ran out and she returned to her gambling behavior, but upon resuming acamprosate she again stopped gambling entirely. In a case study published in November , Pettorruso et al. Unlike previous studies, this was the first to examine amantadine in patients without comorbid Parkinson's disease PD.
In addition to PG, the patient also endorsed AD, nicotine dependence, opioid dependence, and cocaine abuse. At intake, the patient was also experiencing a major depressive episode. The patient was admitted to a treatment program where he was treated for his depression, alcohol withdrawal and sleep disturbances while attending group sessions to manage his PG. One month into treatment, he was improved on all disorders with the exception of his gambling. In this first study of lithium in treating PG, Moskowitz et al.
All three patients responded to the treatment, but it was many years later until the first RCT was conducted to evaluate lithium in the treatment of PG. In a case study reported by Dell'Osso and Hollander in , a year-old woman presented to their program with severe PG and cyclothymia She reported gambling to help relieve her depressed mood. Her gambling, though controlled at first, quickly intensified.
Her condition improved significantly as determined by her scores on the PG-YBOCS and CGI at study end as compared to baseline the authors did not note either scores in their published article. By the last week of the trial, the patient reported no gambling. The improvement in her gambling coincided with improvement in her affective stability.
Black et al. Eight subjects were enrolled in the week study and had at least one visit after baseline one dropped out after the first week, one after five weeks and one after eight weeks. Five subjects completed the study. All subjects had a two-week observation period prior to starting the medication.
The final dosage was determined by subject's response to medication and any adverse effects. By the final two weeks of the study, five subjects were abstinent from gambling. There were several adverse effects among seven of the eight subjects, with somnolence being the most common.
Limitations include the small sample size, lack of placebo control, exclusion of individuals with co-occurring disorders, and short length of trial. In a case study using carbamazepine, Haller and Hinterhuber described the positive results they obtained when treating a single patient who failed to respond to conventional treatment behavior therapy, psychoanalysis, GA Multiple cases in which PG is being treated with atypical antipsychotic drugs involve patients with Parkinson's disease PD , some of whom developed PG after being started on dopamine replacement therapy for PD.
As this is a unique subset of individuals with PG, findings with treatments used in this population may not extend to the general population. Consistent with this notion, there have been several RCTs of PG subjects without PD who have been treated with antipsychotics, and these trials have been negative 30 - In one case of treating PG reportedly emerging following dopamine agonist treatment of PD, Seedat et al.
She was treated with 1mg daily risperidone in addition to her PD medications. Her gambling behavior ceased altogether four weeks after the addition of risperidone. The next case report involves a year-old male who was admitted to inpatient treatment for gambling problems and jealous delusions six months after beginning 3. After 10 weeks, his PG behavior remitted and his delusional behavior was also significantly improved. There was no adverse impact on his PD.
This was the first reported case of quetiapine in the treatment of PG. Rotondo et al. In all three cases, SSRIs were initially prescribed to target gambling behaviors with no apparent success. They switched from SSRIs to clozapine and in two of three cases, problem-gambling symptoms remitted. All three cases had past histories of major depression and alcohol abuse, although all were in remission for several years.
Though not treated with antipsychotics, two additional case reports of PD patients who developed PG on dopamine agonists are reported by Kurlan They are reviewed here as they presented with PG only after being treated for their PD symptoms. The first report involves a year-old male who developed PG over several years.
The prescriber tried to discontinue one of his daily PD medications pramipexole without effect, prescribed modafinil to treat sedation again without effect , and finally tried citalopram, which helped with his depression, but did not alleviate his gambling. The patient began attending GA sessions and reported a significant reduction and finally abstinence in his gambling behavior. In the second case, a year-old woman developed PG after being treated for her PD.
Discontinuation of her PD medications had no effect on her gambling. The authors did not report on additional treatment options. Naltrexone is an opioid receptor antagonist used primarily to treat alcohol and opioid dependence. Adverse effects include headaches, nausea, diarrhea, constipation, dry mouth, insomnia, and dizziness.
The first case study exploring naltrexone in the treatment of PG was described by Crockford and el-Guebaly in The report described a case study of a year-old male with AD and PG. By the end of the first 48 hours, he had a cessation in his craving for alcohol and gambling.
No relapses were noted during the four-week period he was on naltrexone. The next case study was described by Kim in In this case, a year-old male with severe PG and compulsive shopping presented. Kim and Grant next conducted an open-label trial of naltrexone to test its efficacy and tolerability for further testing Seventeen patients were enrolled into 6-week, open-label, flexible-dose trial of naltrexone for treating PG.
Fourteen patients completed the study, and all 17 were included in the intent-to-treat analysis. Adverse effects included nausea, diarrhea, drowsiness, and insomnia. Significant improvement on all measures was noted across all subjects, with the therapeutic effects emerging between one to four weeks.
Recently, an individual with PG reported increased anxiety, vivid dreams, a feeling of doom, and racing thoughts after two doses of 25 mg oral naltrexone. This physically healthy, middle-aged male with DSM-IV PG was enrolled in a double blind, placebo-controlled clinical trial of naltrexone treatment concomitant with treatment as usual TAU through a problem-gambling treatment program.
He met eight of ten inclusionary criteria for PG and reported gambling to escape from stressors in his life. The patient had a history of self-reported anxiety over his gambling behavior and how it affected his life, though it failed to reach threshold for a diagnosis of anxiety disorder.
The patient also reported intermittent suicidal thoughts and trouble sleeping due to his gambling-related problems. He reported going for a walk, which he reported did not help much, although eventually he was able to go back to sleep. The patient discontinued the medication, reported improvement and denied any effects after the following day. The patient continued with the TAU component of treatment. No similar episodes of racing thoughts and anxiety were reported.
These findings complement those of a panic attack related to naltrexone dosing in a woman with anorexia nervosa and also resonate with observations of manic features following naltrexone treatment during heroin detoxification 41 , The data reported here complement those reviewed recently describing pharmacological treatments for PG 1. The pharmacological treatment algorithm proposed in that article still appears relevant.
In this algorithm, clinicians can determine which treatment course may best serve their clients by answering yes or no questions largely related to co-occurring psychiatric conditions, leading to the most appropriate treatment option. Specifically, if patients are less willing to take a pharmacological drug but are more willing to take an over-the-counter health supplement or neutraceutical, then n-acetyl cysteine might be considered. If the patient is willing to take a medication, the best available data support the use of an opioid antagonist like naltrexone, particularly in individuals with a familial history of alcoholism or strong gambling urges at treatment onset.
However, if the patient has a cycling mood disorder, then a mood-stabilizing agent like lithium appears indicated. On the other hand, some data support the use of a serotonin reuptake inhibitor like escitalopram for co-occurring anxiety disorders and PG, although this approach and others in the algorithm warrants additional investigation. In addition, lines of future study e. As recent studies have begun to examine individual differences in biological and behavioral features that may relate importantly to treatment outcome, the goal of more precisely matching treatments with specific people seeking treatment remains an important and perhaps more attainable prospect.
Research into the molecular genetics of PG has mainly focused on familial links and alleles implicated in dopaminergic and serotonergic dysfunctions No genetic variants have been definitively linked to PG. However, treatment outcome in response to some medications showing efficacy in the treatment of PG have been linked in the treatment of other disorders with genetic variations e. Thus, the extent to which such polymorphisms might relate to treatment outcome to naltrexone treatment in PG warrants consideration.
Future studies may also consider identifying genetic variants for traits such as impulsiveness, compulsiveness, or sensation-seeking that are associated with PG as these may provide important information to target specific medications to specific subsets of people with PG. Several of the trials reviewed here noted comorbidities such as SUDs, an important consideration when determining a treatment course.
As noted in our original article, some clinical trials for PG were based on findings in SUDs and, as such, these treatments, especially when combined with behavioral therapy, may be helpful for people with co-morbid PG and SUDs.
The views presented here do not necessarily reflect those of the funding agencies, and the work was generated solely by the contributing authors. Conflicts of Interest: The authors report that they have no financial conflicts of interest with respect to the content of this manuscript. Potenza has received financial support or compensation for the following: Dr.
Bullock reports no biomedical financial interests or other conflicts of interest. National Center for Biotechnology Information , U. Curr Psychopharmacol. Author manuscript; available in PMC Nov 5. Scott A. Bullock 1 and Marc N. Potenza 1, 2. Marc N. Author information Copyright and License information Disclaimer. Copyright notice. See the article " Biotin-binding proteins and biotin transport to oocytes.
See other articles in PMC that cite the published article. Abstract This is an update to a previously published article discussing the neuropsychopharmacology of pathological gambling PG 1. Background With the publication of the DSM-5, changes to the classification and diagnostic criteria for PG have been introduced.
Serotoninergic Clomipramine Clomipramine is a tricyclic antidepressant TCA that works by increasing in the brain the activity of serotonin and norepinephrine, two neurotransmitters implicated in PG. Clomipramine and Modafinil Modafinil is a dopamine agonist, increasing cortical concentrations of dopamine.
Nefazodone Nefazodone is synthetically derived phenylpiperazine antidepressant. Dopaminergic Bupropion Bupropion, a drug with documented efficacy in the treatment of depression and nicotine dependence, belongs to an aminoketone class of drugs and is related to phenylethylamines. Disulfiram Disulfiram may alter the relative balance of dopamine and norepinephrine in the central nervous system through its effects on dopamine beta-hydroxylase Topiramate In a case study out of Brazil, Nicolato et al.
Acamprosate In the only report of acamprosate in the treatment of PG, Raj described a case study of a year-old woman with a long history of depression who presented to his clinic in May for treatment of depressive symptoms Amantadine In a case study published in November , Pettorruso et al.
Carbamazepine Black et al. Opioid Antagonists Naltrexone Naltrexone is an opioid receptor antagonist used primarily to treat alcohol and opioid dependence. Conclusions and Future Directions The data reported here complement those reviewed recently describing pharmacological treatments for PG 1.
Footnotes Conflicts of Interest: The authors report that they have no financial conflicts of interest with respect to the content of this manuscript. References 1. Pathological Gambling: Neuropsychopharmacology and Treatment. Current Psychopharmacol. J Gambl Stud.
Altered brain activity during reward anticipation in pathological gambling and obsessive-compulsive disorder. PLoS One. Compulsive features in behavioural addictions: the case of pathological gambling. Do pathological gambling and obsessive-compulsive disorder overlap? View tocasino. Best Offers and exclusive offers! Lucky Rose; Lucky Ladys Charm Where are all the singles in Asia?
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