naloxone and Bipolar-Disorder

Buprenorphine and naloxone (Suboxone) is a combination medication-assisted treatment (MAT) for opioid use disorder. MAT withdrawal-induced psychosis is a rare clinical presentation. To our best knowledge, only three reports have summarized the characteristic manifestations of buprenorphine withdrawal psychosis, yet all of them were male. In this case report, we present a 41-year-old female patient with bipolar disorder and comorbid substance use disorder who developed new-onset psychosis and relapse of manic symptoms following abrupt discontinuation of Suboxone. Manic and psychotic symptoms remitted after a short-term hospitalization with the treatment of an antipsychotic and a mood stabilizer. In addition to discussing this case presentation and treatment approach, we review existing literature and discuss possible underlying mechanisms to enhance understanding of this clinical phenomenon.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Male; Naloxone; Psychotic Disorders; Substance Withdrawal Syndrome

Topics: Bipolar Disorder; Female; Glasgow Coma Scale; Humans; Middle Aged; Naloxone; Poisoning; Renal Dialysis; Suicide, Attempted; Valproic Acid

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Growth Hormone; Humans; Hydrocortisone; Methylphenidate; Models, Psychological; Naloxone; Prolactin; Schizophrenia

Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Depressive Disorder; Endorphins; Humans; Hydrocortisone; Male; Methadone; Middle Aged; Naloxone; Narcotics; Prolactin; Schizophrenia

Topics: Animals; Behavior, Animal; Bipolar Disorder; Brain; Depression; Endorphins; Humans; Naloxone; Pituitary Gland; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors; Receptors, Opioid; Schizophrenia

Topics: Anxiety; Bipolar Disorder; Deficiency Diseases; Depression; Endorphins; gamma-Aminobutyric Acid; Humans; Mental Disorders; Naloxone; Schizophrenia

The rate of substance-use disorders in patients with mental illnesses within the psychotic spectrum, such as schizophrenia, schizoaffective disorder, and bipolar disorder, is higher than the rate observed in the general population and is associated with significant morbidity and mortality. Although there are currently 3 medications approved by the Food and Drug Administration for the treatment of alcohol dependence, no medications have been approved for the specific treatment of dually diagnosed patients. A small but growing body of literature supports the use of 2 of these medications, disulfiram and naltrexone, in dually diagnosed individuals. This article outlines a review of the literature about the use of disulfiram and naltrexone for alcoholism and in patients with comorbid mental illness. In addition, results are presented of a 12-week randomized clinical trial of disulfiram and naltrexone alone and in combination for individuals with Axis I disorders and alcohol dependence who were also receiving intensive psychosocial treatment. Individuals with a psychotic spectrum disorder, including schizophrenia, schizoaffective disorder, and bipolar disorder, had worse alcohol outcomes than those without a psychotic spectrum disorder. Individuals with a psychotic spectrum disorder had better alcohol-use outcomes on an active medication compared with placebo, but there was no clear advantage of disulfiram or naltrexone or of the combination. Retention rates and medication compliance in the study were high and exceeded 80%. Pharmacotherapeutic strategies should take into account the advantages and disadvantages of each medication. Future directions of pharmacotherapeutic options are also discussed.

Topics: Adult; Alcohol Deterrents; Alcoholism; Bipolar Disorder; Combined Modality Therapy; Comorbidity; Diagnosis, Dual (Psychiatry); Disulfiram; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Motivation; Naloxone; Narcotic Antagonists; Psychotic Disorders; Schizophrenia; Treatment Outcome; Veterans

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

The behavioral effects of a 2 mg/kg iv bolus infusion of naloxone were compared with a placebo infusion using a double-blind design in a small group of inpatient depressives (n = 6) and normals (n = 8). Naloxone produced consistent and significant worsening in the rated signs and subjective symptoms of depression in the patients. In the normals, lesser changes in Hamilton depression and BPRS total scores were observed while none of the subjective scales were significantly altered. The data suggest that depressives manifest a more marked and subjectively more intense response to naloxone compared to normals. Further studies are required to confirm this preliminary finding and to clarify its relationship to the pathogenesis of depression.

Topics: Adult; Bipolar Disorder; Depressive Disorder; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Growth Hormone; Humans; Hydrocortisone; Methylphenidate; Models, Psychological; Naloxone; Prolactin; Schizophrenia

A double-blind study of the behavioral effects of short-term naloxone hydrochloride administration was performed in 32 schizophrenic and 26 manic patients in a World Health Organization collaborative project. There was a significant naloxone-associated reduction in overall physician-rated symptoms in schizophrenic patients concurrently treated with neuroleptic medication (N = 19) but not in medication-free schizophrenics (N = 13). Physician rating of auditory hallucinations showed significant naloxone-associated improvement for the total schizophrenic population, while self-ratings of auditory hallucinations showed improvement only in neuroleptic-treated schizophrenics. While further studies are needed to delineate these effects as to clinical significance, they may bear etiological implications for the psychobiology of schizophrenia, including the possibility of synergistic effects of dopamine and endorphin blockade. Naloxone produced no significant behavioral effects in manic patients. These findings are discussed with relationship to the hypotheses of endorphin involvement in schizophrenia and mania.

Topics: Adult; Affective Disorders, Psychotic; Aged; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; World Health Organization

Topics: Adult; Bipolar Disorder; Brief Psychiatric Rating Scale; Double-Blind Method; Female; Hallucinations; Humans; Injections, Subcutaneous; Male; Middle Aged; Naloxone; Schizophrenia

Topics: Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Naloxone; Naltrexone; Psychotic Disorders; Receptors, Opioid; Schizophrenia

Eleven schizophrenic and three manic patients were randomly administered 0.3 mg/Kg b.wt. of naloxone or placebo in a drug-free state using a double blind procedure. BPRS and CGI were employed for making periodic assessment of mental status; the MRS was additionally used for manic patients. The authors discuss their findings, which are essentially negative.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Schizophrenia

Intravenous naloxone hydrochloride (20 mg) was administered to eight normal control subjects and 12 affective disorder patients manifesting manic or hypomanic symptoms. On two consecutive days, in a counterbalanced order, naloxone and placebo were given in a double-blind crossover design. The overall effect of naloxone was to decrease pulse rate and to promote lethargy and inactivation. The normal controls manifested reduced feelings of well-being, and the manic patients noted a subjective sense of slowing. There was a variable response pattern to naloxone in the manic patients in which four of the 12 patients manifested an observable reduction in their manic symptoms and behavior after the naloxone administration. Naloxone seems to have had a nonspecific subduing effect in both normal subjects and patients and may also have had a selectively greater effect in a small subsample of the manics.

Topics: Adult; Affect; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales; Pulse

Topics: Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Female; Growth Hormone; Humans; Male; Naloxone; Placebos; Psychiatric Status Rating Scales

A 76-year-old woman being treated with sodium valproate for bipolar depression presented with a 4 day history of acute confusion and tremulousness. She had apnoeic episodes, reduced conscious level and generalised myoclonic movements. Her plasma valproate concentration was 848 micromol/l (normal 300-600 micromol/l). Administration of naloxone 0.8 mg led to rapid clinical improvement. Naloxone may be useful in reversing the features of chronic valproate toxicity.

Topics: Aged; Antimanic Agents; Bipolar Disorder; Female; Humans; Naloxone; Narcotic Antagonists; Poisoning; Valproic Acid

Hepatitis C virus (HCV) is the most prevalent chronic viral illness in the United States. Many individuals with virus HCV are opioid dependent requiring treatment with opiate substitution treatment such as buprenorphine. Previous reports in the literature have suggested hepatotoxicity with buprenorphine tempering initial enthusiasm of the safety of buprenorphine in HCV-infected patients.. As part of an ongoing SAMHSA-funded grant to expand opiate substitution therapy with buprenorphine, all opioid-dependent patients seeking treatment with buprenorphine undergo a laboratory evaluation including transaminases (AST/ALT) as well as laboratory evaluation for acute and chronic hepatitis.. Of the 121 patients screened for entry into buprenorphine treatment, 4 patients had evidence of acute HCV infection.. Despite markedly elevated transaminases in the setting of acute hepatitis C infection, these patients tolerated buprenorphine treatment with improvement in their transaminases during the course of buprenorphine treatment.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Bipolar Disorder; Buprenorphine; Cocaine-Related Disorders; Female; Hepatitis B virus; Hepatitis C; Humans; Liver; Liver Function Tests; Male; Naloxone; Narcotic Antagonists; Needle Sharing; Opioid-Related Disorders; RNA, Viral; Transaminases

Topics: Bipolar Disorder; Desensitization, Psychologic; Endorphins; Fear; Female; Humans; Male; Naloxone; Phobic Disorders

Beta-Endorphin (0.3 or 0.6 nanomoles) was infused into the A10-ventral tegmental area (VTA) of male Wistar rats previously treated for 6 days with either morphine sulfate or lactose via subcutaneously implanted silastic pellets. Beta-Endorphin microinfusions occurred at 24 and 96 hours after pellets were removed. Profound changes in locomotor response to beta-endorphin were found, with morphine-pretreated rats showing a spontaneous switch from hyporesponsiveness to hyperresponsiveness over 72 hours, compared to lactose-pretreated controls. These findings may reflect on current biochemical theories regarding the "switch" process in bipolar affective disease. The data can be viewed within a heuristic model of receptor changes which may underlie the transition from depression to mania.

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Dextroamphetamine; Disease Models, Animal; Endorphins; Humans; Limbic System; Male; Morphine; Motor Activity; Naloxone; Neural Pathways; Rats; Rats, Inbred Strains; Receptors, Dopamine; Substance Withdrawal Syndrome; Tegmentum Mesencephali

Cortisol levels were measured before and after administration of naloxone-HCl in patients with affective disorder (n = 16) and normal control subjects (n = 8). On two consecutive days, 20 mg of naloxone-HCl or placebo was administered i.v. over 15 minutes in a double-blind crossover design. Blood samples were collected at 30, 15, and l minute(s) both before and after infusion. Cortisol rose from a mean baseline level of 14.8 microgram% to a mean peak level of 23.1 microgram% following the naloxone administration. Significant cortisol increases were found in both the 15- and 30-minute samples during the naloxone session. There were no differences between patient and normal subject samples or between diagnostic groups. A subgroup of manic patients who had responded to naloxone with a reduction of their manic behavior also had an attenuated cortisol response to naloxone. This proved to be an artifact secondary to variability in the cortisol response in these patients.

Topics: Adult; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Mood Disorders; Naloxone

Since 1975, different morphinomimetic peptides have been isolated from hypophyseal-hypothalamic extracts: the pentapeptides methionine-enkephalin and leucine-enkephalin, and the longer peptides alpha-, beta- and gamma-endorphin. The primary structure of most of these peptides is also present in that of beta-lipotropin. The morphinomimetic properties of endorphins can be blocked with opiate-antagonists. In rats, moreover, the endorphins influence behavior which cannot be blocked with opiate antagonists. On the basis of the hypothesis that hyperactivity of endorphin systems may be involved in the pathogenesis of schizophrenia and manic syndromes, the effect of opiate antagonists on psychotic and manic symptoms has been examined in a number of clinical studies in the past few years. A transient therapeutic effect has been demonstrated in about 30% of the patients so treated. Our own double-blind controlled study of 5 schizophrenic and 5 manic patients in the context of a World Health Organization project failed to reveal any therapeutic effect after subcutaneous injection of 20 mg naloxone. The possible reasons of the negative results are discussed.

Topics: Affective Disorders, Psychotic; Bipolar Disorder; Double-Blind Method; Endorphins; Hallucinations; Humans; Naloxone; Schizophrenia

The authors conducted a double-blind placebo-controlled study in which patients with a wide range of manic symptoms were administered 20 mg of naloxone subcutaneously. Naloxone failed to improve manic severity, activation-arousal, or elation-grandiosity for intervals up to 3 hours. Global nurse ratings of mania did not improve over an 8-hour period. The authors suggest that the question of endorphin involvement in mania has not been resolved and recommend clinical studies with longer acting oral narcotic antagonists such as naltrexone.

Topics: Affective Disorders, Psychotic; Bipolar Disorder; Double-Blind Method; Humans; Naloxone; Psychotic Disorders

Topics: Bipolar Disorder; Endorphins; Enkephalins; Humans; Naloxone; Nociceptors; Pain; Schizophrenia

Topics: Adult; Amphetamine; Bipolar Disorder; Cocaine; Dopamine; Endorphins; Euphoria; Heroin Dependence; Humans; Lithium; Male; Methadone; Naloxone; Prolactin; Receptors, Opioid