naloxone and Depressive-Disorder

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Depressive Disorder; Drug Therapy, Combination; Endorphins; Enkephalins; Humans; Mental Disorders; Naloxone; Naltrexone; Nerve Tissue Proteins; Pituitary Hormones; Psychotropic Drugs; Schizophrenia; Substance-Related Disorders; Vasopressins

Endorphinergic neurons certainly play a role in the brain's processing of painful stimuli. Endorphins act to alter pain appreciation at many levels within the central nervous system including spinal cord, midbrain, thalamus, and cortex. The activity of this pain-suppressing system may play a role in individual differences in the experience of pain. Endorphinergic mechanisms play a major role in analgesia associated with stress and acupuncture, and perhaps mediate placebo-induced analgesia. Chronic pain influences endorphinergic function perhaps depleting endorphinergic neurons of their neurotransmitters. Endorphin function and pain sensibility are prominently affected in affective illness and schizophrenia. It may be that endorphinergic neurons play a fundamental role in selective attention--a kind of sensory filtering of information flow--in somatosensory and other sensory modalities.

Topics: Analgesia; Analgesics; Animals; Antidepressive Agents; Attention; Central Nervous System; Circadian Rhythm; Depressive Disorder; Endorphins; Humans; Mice; Naloxone; Neural Pathways; Pain; Schizophrenia; Stress, Physiological; Synaptic Transmission

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

Topics: Depressive Disorder; Endorphins; Humans; Mood Disorders; Naloxone; Narcotics

Endogenous opioid peptides inhibit the hypothalamic-pituitary-adrenal (HPA) axis by influencing the release of hypothalamic corticotropin releasing factors. This study examines whether increased activity of the HPA axis in major depression is associated with reduced opioid tone.. We measured the adrenocorticotropin (ACTH) and cortisol responses to an intravenous bolus of naloxone 0.125 microg/kg in 13 depressed outpatients and 13 healthy volunteers.. The mean cortisol response was significantly reduced (P<0.05), and the ACTH response was also non-significantly reduced in the depressed subjects.. These findings imply that the degree of inhibitory endogenous opioid tone is reduced in depression. Various mechanisms for the finding are discussed, including possible alteration in the function of alpha-adrenergic pathways.. Reduced endogenous opioid tone may explain why some depressed individuals self-medicate with opiates, and depression is associated with opiate withdrawal. Opioid pathways may have a role in the mechanism of action of antidepressant drugs, and may be of relevance in the development of novel antidepressants.. The sample size was small, leading to a failure of the difference of the basal cortisol levels and also the delta ACTH between the groups to reach statistical significance.

Topics: Adrenocorticotropic Hormone; Adult; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Injections, Intravenous; Male; Naloxone; Narcotic Antagonists; Pituitary-Adrenal System; Single-Blind Method

Electroconvulsive therapy (ECT) is a highly effective treatment for major depression, but is also associated with characteristic cognitive side effects. Several reports document that endogenous opioids and their receptors are activated by electroconvulsive shock (ECS) and that naloxone in doses sufficient to block endogenous opioid receptors may reverse ECS-induced retrograde amnesia. This placebo-controlled, randomized, within-patient study was conducted to examine the potential of naloxone, given in doses sufficient to block opioid receptors (high dose), to ameliorate acute anterograde and retrograde memory impairments following ECT. Compared to placebo and low dose naloxone, high dose naloxone administered immediately before ECT resulted in significant reductions in anterograde amnesia, and better performance on an attention task. Both low and high dose naloxone improved verbal fluency. There were no beneficial effects of high dose naloxone on retrograde amnesia, and an indication that high dose naloxone may have worsened retrograde amnesia for shape stimuli. There were no effects of high dose naloxone on seizure duration, vital signs, and subjective side effects. The study is consistent with prior research in which change in behavioral and physiological measures was produced principally by naloxone doses sufficient to block endogenous opioid receptors and offers evidence of the potential for ameliorating some adverse cognitive effects associated with ECT.

Topics: Adult; Aged; Amnesia, Retrograde; Analysis of Variance; Cognition Disorders; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Orientation; Placebos; Seizures; Treatment Outcome

Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

Topics: Adult; Aged; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Injections, Intravenous; Male; Middle Aged; Motor Activity; Naloxone; Narcotic Antagonists; Seizures; Time Factors

Adrenocorticotropic hormone (ACTH) and cortisol secretion have been shown to be abnormal in approximately half of depressed patients. Information from pituitary and adrenal studies suggests that the locus of this dysregulation is at or above the level of the hypothalamus; however, direct evidence from provocative studies of the hypothalamic corticotropin releasing hormone (CRH) neuron does not exist. The current study was designed to stimulate hypothalamic CRH release using the opiate antagonist naloxone in patients with depression and elevated urinary-free cortisols as well as healthy and psychiatric controls. All subjects received naloxone and placebo on separate days in a double-blinded, randomized fashion at a dose determined previously to reliably induce significant increases in ACTH and cortisol secretion. No significant differences were noted among groups. We conclude that although naloxone is an effective central stimulant of the hypothalamic CRH neuron, stimulation of the hypothalamic CRH neuron with naloxone does not provide evidence of dysregulation of the HPA axis in depression.

Topics: Adrenocorticotropic Hormone; Adult; Behavior; Depressive Disorder; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Naloxone; Narcotic Antagonists; Obsessive-Compulsive Disorder; Pituitary-Adrenal System; Stimulation, Chemical

Although there is clear evidence in other species that electroconvulsive therapy (ECT) is associated with changes in endogenous opioid activity, there are few data available for such a role in man. Since ECT leads to changes in certain hormones in man, particularly serum prolactin, it was postulated that such changes may represent an increase in endogenous opioids. Six unmedicated patients with major depressive illness were therefore administered either 4 mg i.v. of the opiate antagonist naloxone or a saline control infusion, just before successive treatments with ECT, in a double-blind, randomized crossover design. Blood was sampled at intervals for serum prolactin, growth hormone (GH), and cortisol. ECT led to a clear rise in serum prolactin, with no significant change seen in either serum GH or serum cortisol during the 20-min sampling interval. Naloxone had no significant effect on any of these changes. It is concluded that the rise in serum prolactin in response to ECT is not mediated by changes in endogenous opioid peptide activity.

Topics: Adult; Aged; Brain; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Electroconvulsive Therapy; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Prolactin; Random Allocation; Receptors, Opioid

The opiate antagonist naloxone has been reported to improve memory in animals and to produce partial improvement in Alzheimer's dementia. The usefulness of naloxone for reversing ECT-induced cognitive impairment was tested by comparing the effects of naloxone and placebo on several tests of cognitive performance in 10 patients who underwent bilateral ECT. No significant differences were found between naloxone and placebo. The results suggest that at the doses used, naloxone is not effective in reversing ECT-induced memory deficits.

Topics: Adult; Aged; Amnesia; Cognition Disorders; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Psychological Tests

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

Studies on sexual functioning of populations with substance use disorders (SUDs) are mostly conducted with male substance users. We have very limited information about the sexuality and related factors in women with opioid use disorder (OUD).. We aimed to evaluate the relationship between childhood traumatic experiences (CTEs) and sexual dysfunctions (SDs) of women with OUD and to compare it with a sample of women who do not have SUD.. Participants included 51 outpatient women with OUD who were on opioid maintenance treatment (OMT) with Buprenorphine/Naloxone and 48 women without SUD. Participants were evaluated by a semi-structured sociodemographic form, the Golombok-Rust Inventory of Sexual Satisfaction (GRISS), the Childhood Trauma Questionnaire (CTQ-28), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI).. In women with OUD; CTQ-28, BDI, STAI, and GRISS scores were significantly higher. In the partial correlation analysis, sexual abuse was found to be significantly correlated with nonsensuality, avoidance and total GRISS score. In stepwise regression model, sexual abuse was found to predict SDs together with depression.. CTE, SD, depression, and anxiety rates were higher in the women with OUD. Especially childhood sexual abuse was associated with SDs in this group. Sexual abuse was predicting SDs together with depression. Further investigation of different characteristics of women with SUD may give an opportunity to clinicians to have a better understanding for adaptable treatment strategies.

Topics: Adult; Anxiety Disorders; Buprenorphine; Case-Control Studies; Child; Child Abuse, Sexual; Depressive Disorder; Drug Therapy, Combination; Female; Humans; Middle Aged; Naloxone; Opioid-Related Disorders; Psychiatric Status Rating Scales; Regression Analysis; Sexual Dysfunctions, Psychological; Surveys and Questionnaires

Animal and clinical researches indicate that the opioid system exerts a crucial role in the etiology of mood disorders and is a target for intervention in depression treatment. This study investigated the contribution of the opioid system to the antidepressant-like action of acute or repeated m-trifluoromethyl-diphenyl diselenide administration to Swiss mice. m-Trifluoromethyl-diphenyl diselenide (50 mg/kg, intragastric) produced an antidepressant-like action in the forced swimming test from 30 min to 24 h after treatment. This effect was blocked by the µ and δ-opioid receptor antagonists, naloxonazine (10 mg/kg, intraperitoneally) and naltrindole (3 mg/kg, intraperitoneally), and it was potentiated by a κ-opioid receptor antagonist, norbinaltrophimine (1 mg/kg, subcutaneously ). Combined treatment with subeffective doses of m-trifluoromethyl-diphenyl diselenide (10 mg/kg, intragastric) and morphine (1 mg/kg, subcutaneously) resulted in a synergistic antidepressant-like effect. The opioid system contribution to the m-trifluoromethyl-diphenyl diselenide antidepressant-like action was also demonstrated in the modified tail suspension test, decreasing mouse immobility and swinging time and increasing curling time, results similar to those observed using morphine, a positive control. Treatment with m-trifluoromethyl-diphenyl diselenide induced neither tolerance to the antidepressant-like action nor physical signs of withdrawal, which could be associated with the fact that m-trifluoromethyl-diphenyl diselenide did not change the mouse cortical and hippocampal glutamate uptake and release. m-Trifluoromethyl-diphenyl diselenide treatments altered neither locomotor nor toxicological parameters in mice. These findings demonstrate that m-trifluoromethyl-diphenyl diselenide elicited an antidepressant-like action by direct or indirect μ and δ-opioid receptor activation and the κ-opioid receptor blockade, without inducing tolerance, physical signs of withdrawal and toxicity.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; Behavior, Animal; Depression; Depressive Disorder; Male; Mice; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Organosilicon Compounds; Receptors, Opioid, kappa; Substance Withdrawal Syndrome; Swimming

Topics: Benzodiazepines; Charcoal; Combined Modality Therapy; Depressive Disorder; Drug Overdose; Female; Flumazenil; Hemoperfusion; Humans; Hyperammonemia; Middle Aged; Naloxone; Olanzapine; Paranoid Disorders; Psychotropic Drugs; Respiration, Artificial; Suicide, Attempted; Valproic Acid

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

Topics: Animals; Chronic Disease; Citalopram; Depressive Disorder; Diazepam; Disease Models, Animal; Flumazenil; GABA Modulators; Male; Mecamylamine; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Stress, Psychological; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Acute Disease; Adult; Depressive Disorder; Humans; Male; Methadone; Naloxone; Narcotic Antagonists; Narcotics; Poisoning; Suicide, Attempted

Topics: Adult; Aged; Depressive Disorder; Electroconvulsive Therapy; Electroencephalography; Female; Humans; Male; Naloxone; Narcotic Antagonists; Preanesthetic Medication; Psychotic Disorders; Treatment Outcome

Thirty seven consecutive applicants to methadone maintenance were assessed for depression and for level of opiate dependence using a 0.8-mg naloxone challenge. Nineteen of the applicants met DSM-III-R criteria for current major depression. At 3-month follow-up, high naloxone challenge test (NCT) scores at intake (high levels of opiate addiction) were found to predict poor program retention and elevated symptoms of depression at follow-up. Reports of heavy current drug use at intake were also associated with poor program retention and with high frequencies of positive urine screens for illicit substances during treatment. Level of addiction and reported amount of drug use at intake independently predicted program retention with a multiple correlation of 0.46 (P less than .01). Although NCT predicted depression at follow-up, depression at intake did not significantly predict treatment outcome, and NCT score predicted outcome independently of psychopathology.

Topics: Arousal; Depressive Disorder; Humans; Methadone; Naloxone; Opioid-Related Disorders; Personality Tests; Prognosis; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome

Plasma prolactin (PRL), cortisol, and growth hormone (GH) were measured before, and at 15-min intervals for 1 hr after, electroconvulsive therapy (ECT). This was repeated over a series of 6 consecutive treatments for each of 12 depressed drug-free inpatients. Patients received naloxone, 2 mg or 20 mg, by intravenous infusion before the third and fifth treatment. ECT was consistently followed by a release of PRL and cortisol, although two patterns of PRL response could be distinguished. In eight patients, the PRL response did not change significantly with repeated ECT, whereas in four patients, the plasma PRL increased tenfold after the first treatment and decreased after each successive treatment. The GH level varied widely, with no evidence of a reliable response to ECT. Opiate receptor blockade with low- or high-dose naloxone did not alter the release of PRL or cortisol after ECT. These findings demonstrate a reliable PRL and cortisol response to ECT, but do not support a role for endogenous opiates in these hormonal changes.

Topics: Adult; Aged; Depressive Disorder; Dose-Response Relationship, Drug; Electroconvulsive Therapy; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Premedication; Prolactin; Psychiatric Status Rating Scales; Psychotic Disorders; Receptors, Opioid

Topics: Adult; Depressive Disorder; Electroconvulsive Therapy; Endorphins; Humans; Middle Aged; Naloxone; Pituitary Gland, Anterior; Prolactin

Topics: beta-Endorphin; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Hydrocortisone; Naloxone; Prolactin; Psychotic Disorders; Psychotropic Drugs; Receptors, Opioid; Schizophrenia

Topics: Adult; Depressive Disorder; Female; Humans; Hydrocortisone; Male; Morphine; Naloxone; Prolactin; Receptors, Opioid

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

Premenstrual and postpartum dysphoric changes are very prevalent. However, their etiology is still obscure. The authors hypothesize that changes in levels of endorphins may be involved in the pathophysiology of these changes. Studies of various endorphins indicate a possible relationship between levels of endorphins and depressive symptoms. In addition, some studies of naloxone and naltrexone suggest a relationship between a blockage in the action of endorphins and the development of a syndrome of dysphoric symptoms similar to the depressive features manifested premenstrually and postpartum by many women and frequently seen in some depressed outpatients. There is also some evidence that there may be a relationship between elevated levels of endorphins and other subtypes of depressive syndromes. Endorphins and estrogen levels have been shown to covary. During the postpartum and the premenstrual period, levels of both change rapidly and substantially. Therefore the link between changes in levels of endorphins and the dysphoric changes during the periods in focus is supported from three complementary directions: (1) the characteristic psychiatric symptomatology, (2) the reported hormonal changes, and (3) the possible involvement of endorphins in neuroendocrine regulation.

Topics: Animals; Behavior; Depressive Disorder; Dopamine; Endorphins; Estrogens; Female; Humans; Naloxone; Neurosecretory Systems; Pain; Pituitary Hormones; Pregnancy; Premenstrual Syndrome; Puerperal Disorders; Rats