[Anhedonia, depression, anxiety, and craving in opioid dependent patients stabilized on oral naltrexone or naltrexone implant]. / Angedoniia, depressiia, trevoga i vlechenie k upotrebleniiu narkotikov u patsientov s opioidnoi zavisimost'iu pri kursovom lechenii peroral'noi ili implantiruemoi formoi naltreksona.

AIM: To assess the relationship between long-term naltrexone treatment and anxiety, depression and craving in opioid dependent individuals. MATERIAL AND METHODS: Opioid dependent patients (n=306) were enrolled in a three cell (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month trial comparing extended release implantable naltrexone with oral naltrexone and placebo (oral and implant). Monthly assessments of affective responses used a Visual Analog Scale for opioid craving, the Beck Depression Inventory, Spielberger Anxiety Inventory, and the Ferguson and Chapman Anhedonia Scales. Between-group outcomes were analyzed using mixed model analysis of variance (Mixed ANOVA) and repeated measures and the post hoc Tukey test. RESULTS AND CONCLUSION: Anhedonia, depression, anxiety, and craving for opiates were elevated at baseline but gradually reduced to normal within the first 1-2 months for patients who remained in treatment and did not relapse. There were no significant between-group differences prior to treatment dropout as well as between those who relapsed and who continued on naltrexone. CONCLUSION: These data do not support concerns that naltrexone treatment of opioid dependence precipitates anhedonia, depression, anxiety or craving for opiates.

[A double-blind randomized placebo-controlled study of the efficacy of the combined treatment with naltrexone and guanfacine for relapse prevention in opiate dependence].

OBJECTIVE: Authors studied the effect of α-2-adrenoreceptor agonist guanfacine on replace prevention in opiate addicts. MATERIAL AND METHODS: Three hundred and one recently detoxified opiate addicts were randomized under the double-blind double-dummy conditions into one of four treatment groups: naltrexone 50 mg/day+guanfacine 1 mg/day (N+G), naltrexone+guanfacine placebo (N+GP), naltrexone placebo+guanfacine (NP+G), and double placebo (NP+GP). The primary outcome was retention in treatment. The secondary outcomes were perceived stress (Perceived Stress Scale) and craving. RESULTS: At the end of six months, 20 (26.7%) patients in the N+G group and 15 (19.7%) (p=0.26 to N+G) in N+GP group were retained in treatment compared to 5 (6.7%) in the NP+G group (p=0.002 to N+G group and p=0.017 to N+GP group) and 8 (10.7%) in the double placebo group (p=0.013 to N+G group). There is no significant difference in retention between the N+G group and N+GP group at the end of treatment. CONCLUSION: Guanfacine had significant craving and stress reducing effect. Naltrexone was more effective than placebo for relapse prevention in opioid dependent patients. The efficacy of the combination of naltrexone and guanfacine was comparable to naltrexone alone. Guanfacine moderately reduced both stress and craving.

[Naltrexone and fluoxetine for maintenance of remission in patients with heroin addiction: a double-blind randomized placebo-controlled trial].

Two hundreds and eighty patients with heroin addiction were randomized into 4 equal groups. Patients of the group 1 received naltrexone (N) in dosage 50 mg/day and fluoxetine (F) in dosage 20 mg/day during 6 months. Group 2 received N/F-placebo (FN), group 3--N-placebo (NP)/F and group 4--NP/FP. All patients underwent a session of individual psychotherapy for the maintenance of remission. Express urine drugs tests were used for remission control. Compliance was controlled by a riboflavin marker. Clinical state, psychiatric status and social functioning were assessed using quantified international scales and tests. To the end of the 6 month course, 43% of patients of group 1, 36% of group 2, 21% of group 3 and 10% of group 4 were in remission. Therefore, N/F was more effective than F/NP (p < 0.01) and FP/NP (p < 0.001); N/FP was more effective than F/NP (p < 0.05) and NP/FP (p < 0.001); F/NP did not differ significantly from NP/FP (p = 0.1); N/F did not differ from N/FP (p = 0.2). However N/F was more effective compared to N/FP only in women, probably, due to the higher baseline levels of depression, anxiety and anhedonia. Naltrexone was superior to placebo and fluoxetine in the efficacy of maintenance of remission and preventing relapse in patients with heroin addiction. The combination of naltrexone and fluoxetine was more effective compared to the monotherapy with naltrexone in women only.

Overcoming opioid blockade from depot naltrexone (Prodetoxon).

AIM: To describe a situation in which an opioid-dependent patient overcame naltrexone blockade. DESIGN, CASE REPORT, SETTING: Addiction treatment center in St Petersburg, Russia. PARTICIPANT: Patient with naltrexone implant. INTERVENTION: Detoxification. MEASUREMENTS: Clinical observations. CONCLUSIONS: It is possible, but very difficult, to overcome naltrexone blockade by using large doses of heroin.

[The relationship between the craving for alcohol and relapse of the disease].

The craving for alcohol was studied using 2 Russian and 4 international scales, including ratings of the clinician and self-rating of the patient. Depression and anxiety as well as the content of alcohol in exhaled air were assessed. The data were compared to the scores of the Impulsive Relapse Questionnaire. Eighteen patients were studied. The prolonged conscious or insurmountable or poorly controlled drive for alcohol was rare in patients in the remission. Most of patients do not notice such a drive though it was found with the corresponding scales. The craving for alcohol is more often caused by the environment factors related as to alcohol as well to non-specific stress factors and represents a transient impulsive phenomenon that leads to the relapse of disease.

[The efficacy of calcium channel blockers in the treatment of affective disorders and pathologic drive for alcohol in patients with alcoholism in the remission period]. / Effektivnost' blokatorov kal'tsievykh kanalov pri lechenii affektivnykh narushenii i patologicheskogo vlecheniia k alkogoliu u bol'nykh alkogolizmom v period remissii.

Forty three patients with chronic alcoholism of stage II with secondary affective disorders (anxiety, subdepression) and actualization of pathological drive for alcohol in remission period were divided into 3 groups: patients were treated with nimodipine (90 mg/day during 10 days), patients were treated with nifedipine (45 mg/day during 10 days) and patients of control group (they received a placebo for 10 days). The study was double blind. The results revealed that both calcium channels antagonists reduced a level of depression measured with the Hamilton scale and Zung test. Ten-day nimodipine (but not nifedipine) course also caused a significant decrease of anxiety evaluated by the Spilberger test. Both medications, being significantly more efficient comparing to placebo, led to desactualization of pathological drive for alcohol in parallel with affective disorders reduction. Because of the absence of the depriming effect of these compounds on CNS as well as of dependence phenomenon, calcium channels antagonists may be used in narcology for stopping secondary affective disorders and actualization of pathological drive for alcohol in remission period.

Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists.

Ketamine blocks the calcium channel associated with N-methyl-D-aspartate (NMDA) glutamate receptors. It has transient behavioral effects in healthy humans that resemble aspects of schizophrenia, dissociative disorders, and ethanol intoxication. Ethanol is an antagonist of both NMDA receptors and L-type voltage-sensitive calcium channels (VSCC) and it has minimal psychotogenic activity in humans. A double-blind placebo-controlled study was conducted that evaluated whether pretreatment with the L-type VSCC antagonist, nimodipine, 90 mg D, modulated ketamine response (bolus 0.26 mg/kg, infusion of 0.65 mg/kg/hr) in 26 ethanol-dependent inpatients who were sober for at least one month prior to testing. This study found that nimodipine reduced the capacity of ketamine to induce psychosis, negative symptoms, altered perception, dysphoria, verbal fluency impairment, and learning deficits. Nimodipine improved memory function, but had no other intrinsic behavioral activity in this patient group. Nimodipine pretreatment attenuated the perceived similarity of ketamine effects to ethanol as well as ketamine-induced euphoria and sedation. However, nimodipine did not reduce the stimulant effects of ketamine. These data suggest that antagonism of L-type VSCCs attenuates the behavioral effects of NMDA antagonists in humans. They support the continued evaluation of nimodipine in the treatment of neuropsychiatric disorders. They also suggest that drugs, such as ethanol, that combine NMDA and L-type VSCC antagonism may have enhanced tolerability without attenuation of their stimulant effects.

Prevention of suicide by naltrexone in a recently detoxified heroin addict.

This case describes a heroin addict who was participating in a placebo-controlled randomized trial of naltrexone as an aid to relapse prevention. The patient tried to commit suicide by taking a heroin overdose after learning that he was HIV-positive. He was on naltrexone at the time and, as a result, survived what would probably have been a fatal overdose. This case demonstrates that naltrexone can have immediate as well as long-term positive effects in persons who are attempting to recover from heroin addiction.

[Effect of pharmacotherapy of affective disorders on the psycho-semantics of alcoholic patients]. / Vliianie farmakoterapii afferentnykh narushenii u bol'nykh alkogolizmom na psikhosemantiku.

90 alcoholic patients (II stage of alcoholism) with secondary affective disorders (anxiety, depression) were divided into 4 groups. The patients of the first group received the GABA receptor ligand baclofen during 3 weeks. Sybazon preparation was used in the second group, while the patients of the third group were treated with amitriptyline. Placebo was applied in the forth group. The clinical psychological tests demonstrated that all drugs caused quite effective relief of affective disorders. Psychosemantic tests application showed that the pharmacotherapy caused positive changes in patients of 1-3 groups. These changes touched on both system of personal estimations and relations of personality to himself and to the world around i.e. psychosemantic sphere. Such changes in psychosemantic sphere were not observed in the 4-th group of patients (placebo). Besides it was revealed that each drug caused some specific changes in psychosemantic sphere. The result obtained were supposed to have some theoretical value in comprehension of brain-psychics relations as well as the applied significance for adequate choice of affective disorders pharmacotherapy of alcoholic patients.

[The use of baclofen for treating affective disorders in alcoholism]. / Primenenie baklofena dlia lecheniia affektivnykh rasstroistv pri alkogolizme.

90 patients with alcoholism stage II suffering from secondary affective disorders (anxiety, depression) were divided into 4 groups: treated with GABA-B-receptor ligand baclofen (group 1), with sibazon (group 2), amitriptylin (group 3), placebo (group 4). As shown by clinical, experimental psychological and electrophysiological examinations, baclofen is not inferior in efficacy to sibazon and amitriptylin, but is free of side effects and complications typical for the above drugs (central deprivation, addiction, etc.). MAO activity was unaffected in all the patients, so were dopamine, serotonin and GABA blood concentrations after the treatment. This does not allow to relate the peripheral metabolism of GABA and monoamines to emergence of secondary affective disorders in alcoholism. The authors think promising to seek for drugs effective against affective disorders among ligands of GABA-B receptors.

Baclofen administration for the treatment of affective disorders in alcoholic patients.

Ninety alcoholic patients with the secondary affective disorders (anxiety, depression) were divided into four groups. Patients in the first group received GABAB receptor ligands (baclofen), those in the second group, diazepam, those in the third group, amitriptyline and those in the fourth group, placebo. The results of clinical, psychological (tests of Spielberger, Zung and MMPI), and electrophysiological (superslow omega-potential) investigations showed that baclofen is an effective drug for affective disturbances in alcoholic patients, with efficacy superior to placebo and equal to diazepam and amitriptyline. At the same time baclofen does not have the side-effects and complications of the latter. Significant changes in platelet MAOB activity and the dopamine, serotonin and GABA concentrations in blood after treatment were not found in the four patient groups. The peripheral matabolism of GABA and monoamines do not seem to be related to the development of secondary affective disorders in alcoholic patients. This investigation encourages the search for drugs acting on the affective psychopathology of GABAB receptor ligands.

[One of the methods of treatment of affective disorders in patients with alcoholism]. / Ob odnom iz metodov lecheniia affektivnykh narushenii u bol'nykh alkogolizmom.

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients.

In a double blind placebo-controlled investigation it was shown that transcranial electric treatment (TET), comprising the combination of a constant current with a pulse current of square impulses of 70-80 Hz is an effective method to correct affective disturbances (anxiety, depression) in alcoholic patients. The medical effects of TET are accompanied by changes in the metabolism of GABA and monoamines, but not of beta-endorphin, and also by a decrease in the latency of alpha-rhythm appearance after closing of the eyes.