A Review of the Literature of Mirtazapine in Co-Occurring Depression and an Alcohol Use Disorder.

BACKGROUND: Prior medication studies involving individuals with major depression in combination with an alcohol use disorder (MDD/AUD) have mainly focused on SSRI and tricyclic antidepressants, with generally ineffective results. Consequently, effective treatments for that common comorbid condition remain elusive. Mirtazapine is an antidepressant medicine with a unique pharmacological profile, whose effectiveness for treating non-comorbid depression reportedly may exceed that of SSRIs. OBJECTIVE/METHODS: We now review the published literature regarding the tolerability and efficacy of mirtazapine for the treatment of the depression and the pathological alcohol ingestion of individuals with co-occurring MDD/AUD, including a review of four of our own small studies and two studies conducted outside the United States. RESULTS/CONCLUSIONS: The findings of these studies suggest that mirtazapine is well tolerated among persons with comorbid MDD/AUD. Results also provide some evidence of efficacy for mirtazapine for decreasing the level of depression of persons with co-occurring MDD/AUD, and suggest that decreases in depression may occur relatively quickly after starting treatment, but provide no evidence of effectiveness for decreasing the level of alcohol ingestion. Large-scale double-blind, placebo-controlled studies are warranted to further clarify the tolerability and efficacy of mirtazapine among individuals with MDD/AUD.

Low expression of Abelson interactor-1 is linked to acquired drug resistance in Bcr-Abl-induced leukemia.

The basis for persistence of leukemic stem cells in the bone marrow microenvironment remains poorly understood. We present evidence that signaling cross-talk between α4 integrin and Abelson interactor-1 (Abi-1) is involved in the acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl-positive leukemia cells. Comparison of Abi-1 (ABI-1) and α4 integrin (ITGA4) gene expression in relapsing Bcr-Abl-positive CD34+progenitor cells demonstrated a reduction in Abi-1 and an increase in α4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi-1 and α4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate -resistant leukemic cells. These results indicate that the α4-Abi-1 signaling pathway may mediate acquisition of the drug-resistant phenotype of leukemic cells.

The prevalence of phenotypic subgroups in Greek women with polycystic ovarian syndrome.

BACKGROUND: Since 2003, when the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) sponsored consensus established criteria for polycystic ovarian syndrome (PCOS) diagnosis, the phenotypic spectrum of the syndrome has been significantly broadened. PURPOSE OF THE STUDY: This survey makes an effort to distinguish PCOS according to phenotypic expression and to estimate its prevalence in a Greek population. MATERIALS AND METHODS: Greek women from 18 to 35 years of age, who visited the outpatient department, claiming either irregular menstruation (oligo- or anovulation, OA) or clinical manifestations of hyperandrogenemia (HA) were recruited. They gave full disease history and underwent clinical examination, including transvaginal ultrasound (TVUS) scan to identify PCO morphology. Blood samples were collected to perform hormonal and metabolic analyses. Acute or chronic disorders were excluded. Finally, 266 PCOS women constituted the study population. CONCLUSIONS: The full-blown phenotype (HA+OA+PCO) is the predominant phenotype in this Greek population.

Computerized analysis of fetal heart rate variability using the matching pursuit technique as an indicator of fetal hypoxia during labor.

OBJECTIVE: To determine whether the computerized analysis of fetal heart rate variability with the new matching pursuit technique can indicate fetal distress during labor. STUDY DESIGN: Eighty women were studied during the intrapartum period with external cardiotocography. In all cases, cord arterial pH and 5-min Apgar Scores were evaluated. Six cases that presented large segments of missing data were excluded from the study. The remaining 74 women were divided into two groups; 32 women with normal (Group A) and 42 women with non-reassuring FHR tracings (group B). Group B was divided in subgroup BI, including 24 women with pH > 7.20, and BII, including 18 women with pH < 7.20. In order to evaluate the FHR fluctuations, in different frequency ranges, we applied an adaptive time-frequency method, called Matching Pursuit. We estimated the power of the FHR signal in four frequency ranges. RESULTS: The 5-min Apgar Scores were significantly lower in both subgroup BI and subgroup BII (p = 0.003 and p = 0.003 respectively). The Low Low Frequency (LLF) parameter appears to recognize better the cases with lower pH (sensitivity 78.5%, specificity 52.3%) than the cases with non-reassuring FHR (66.6%, 56.2). The sensitivity and specificity of the Very Low Frequency (VLF) parameter were 72.2% and 59% respectively in recognizing the cases with lower pH and 64.2% and 53.1% in recognizing non-reassuring FHR. CONCLUSION: Fetal hypoxia during labor can be recognized using the MP technique for the analysis of FHR signal power in the VLF and LLF frequency ranges. Since the analysis is feasible in real-time, it can be a useful tool for the intrapartum evaluation of fetal well-being.

Evaluation of non-reassuring fetal heart rate patterns with fetal pulse oximetry combined with vibratory acoustic stimulation.

OBJECTIVE: To determine the value of fetal pulse oximetry and vibratory acoustic stimulation in the presence of non-reassuring fetal heart rate patterns during labor. DESIGN: Prospective study in women monitored by cardiotocography and fetal pulse oximetry during labor. MATERIALS AND METHODS: During a period of 18 months, 907 consecutive parturients in labor were monitored by cardiotocography. Out of these women, 63 were selected on the basis of a non-reassuring fetal heart rate tracing during the first stage of labor. In these cases, fetal pulse oximetry was applied. Vibratory acoustic stimulation was applied in fetuses without spontaneous reactivity in order to evaluate the fetal status. RESULTS: Our cases were classified into three groups, according to the lower fetal oxygen saturation levels, from the time of oximetry application until delivery. Group A consisted of 29 cases where fetal oxygen saturation levels were > or = 41%, group B (20 cases) with fetal oxygen saturation of 31-40% and group C (14 cases) with levels of < 30%. Spontaneous reactivity was observed in 15 fetuses of group A and seven of group B, while no case of reactivity was noted in group C. Vibratory acoustic-induced reactivity was associated with low fetal oxygen saturation levels. The mean umbilical artery pH levels were 7.29 +/- 0.051 in group A, 7.21 +/- 0.057 in group B and 7.04 +/- 0.05 in group C. CONCLUSION: Fetal pulse oximetry should be indicated not only in fetuses without any reactivity but also in those with induced reactivity, after the application of vibratory acoustic stimulation.

Computerised intrapartum diagnosis of fetal hypoxia based on fetal heart rate monitoring and fetal pulse oximetry recordings utilising wavelet analysis and neural networks.

OBJECTIVE: To develop a computerised system that will assist the early diagnosis of fetal hypoxia and to investigate the relationship between the fetal heart rate variability and the fetal pulse oximetry recordings. DESIGN: Retrospective off-line analysis of cardiotocogram and FSpO2 recordings. SETTING: The Maternity Unit of the 2nd Department of Obstetrics and Gynaecology, Aretaieion Hospital, University of Athens. POPULATION: Sixty-one women of more than 37 weeks of gestation were monitored throughout labour. METHODS: Multiresolution wavelet analysis was applied in each 10-minute period of second stage of labour focussing on long term variability changes in different frequency ranges and statistical analysis was performed in the associated 10-minute FSpO2 recordings. Self-organising map neural network was used to categorise the different 10-minute fetal heart rate patterns and the associated 10-minute FSpO2 recordings. MAIN OUTCOME MEASURES: Umbilical artery pH of < or = 7.20 and Apgar score at 5 minutes of < or = 7 formed the inclusion criteria of the risk group. RESULTS: After using k-means clustering algorithm, the two-dimensional output layer of the self-organising map neural network was divided into three distinct clusters. All the cases that mapped in cluster 3 belonged in the risk group except one. The sensitivity of the system was 83.3% and the specificity 97.9% for the detection of risk group cases. CONCLUSIONS: A relationship between the fetal heart rate variability in different frequency ranges and the time in which FSpO2 is less than 30% was noticed. Fetal pulse oximetry seems to be an important additional source of information. Computerised analysis of the fetal heart rate monitoring and pulse oximetry recordings is a promising technique in objective intrapartum diagnosis of fetal hypoxia. Further evaluation of this technique is mandatory to evaluate its efficacy and reliability in interpreting fetal heart rate recordings.

Comorbid alcoholism and depression: treatment issues.

Unless there is decisive professional intervention, people who suffer from both a depressive disorder and alcoholism are at great risk of chronic impairment, both at home and in the workplace; persistent symptomatic misery; and premature death. Untreated alcoholism intensifies depressive states, decreases responsiveness to conventional therapeutics, and increases the likelihood of suicide, suicide attempts, and other self-destructive behavior. During the past decade, evidence has emerged from placebo-controlled studies supporting the utility of tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) for treatment of depressed alcoholics. The superior safety and tolerability of SSRIs provide strong justification for their first-line use despite higher drug acquisition costs. Evidence has similarly emerged concerning the use of several novel pharmacotherapies and focused psychotherapies for people with alcoholism. These newer therapeutic options complement more traditional intervention such as chemical dependence counseling, disulfiram, and Alcoholics Anonymous so that it is now possible for a majority of depressed alcoholics to be treated effectively. The availability of effective treatments provides further impetus for health care professionals to improve recognition of comorbid alcoholism and depressive disorders. Improved recognition and treatment will save lives, and the benefits are likely to extend across generations.

Fluoxetine in adolescents with major depression and an alcohol use disorder: an open-label trial.

Recently, a first placebo-controlled study of an selective serotonin reuptake inhibitor (SSRI) medication was conducted among a sample of adolescents with major depression by Emslie et al. [Arch. Gen. Psychiatry 54 (1997) 1031.]. That study demonstrated efficacy for fluoxetine vs. placebo for treating adolescents with major depression. However, to date, no studies have been conducted to assess the efficacy of fluoxetine or any other SSRI medication in adolescents with major depression in combination with an alcohol use disorder (AUD). In this study, the authors investigated whether fluoxetine decreases the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD. The authors conducted a 12-week open-label study of fluoxetine (20 mg) in 13 adolescents with current comorbid major depression and an AUD. A significant within-group decrease (improvement) was found for both depressive symptoms and drinking during the course of the study. The fluoxetine was well tolerated during the study. These data suggest promise for fluoxetine for decreasing both the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD.

Predictive validity of the physical disorders axis of the DSM multiaxial diagnostic system.

This paper reports on the predictive validity of the physical disorders axis (axis III) of the DSM multiaxial diagnostic system at 3-year follow-up. A total of 515 general psychiatric patients were assessed with a semistructured procedure that covers all DSM-III diagnoses and axes, and were subsequently followed up for 3 years. Outcome was assessed with several measures of adaptive functioning. Baseline axis III was analyzed according to a) presence of any physical disorder, b) the number of these, c) presence of major chronic physical disorders (MCPD), and d) the number of these. Prediction of impairment in functioning (Strauss-Carpenter Scale), derived from baseline axis III, ranged from a correlation coefficient of .18 when expressed as the presence of any physical disorder to .35 when represented by the number of MCPD. Furthermore, within patients with specific psychiatric disorders, it was found that number of MCPD reached a predictive validity of .55 for patients with dysthymic disorders, .44 for those with anxiety disorders, and .41 for those with major depression. Comparative multiple regression analyses, controlling for demographic and clinical variables, showed that the number of MCPD at baseline was the most important predictor of functioning outcome among patients with dysthymic disorders and major depression. The number of MCPD experienced by general psychiatric patients seems to be an important predictor of future functioning, particularly for patients with certain psychiatric disorders. This points out the importance of considering the relationship between psychiatric and MCPD when conducting systematic clinical assessments towards the prediction of course and outcome.

Characterizing female bipolar alcoholic patients presenting for initial evaluation.

This study examined gender differences of age and race-matched group of bipolar disorder (BPO) patients with comorbid alcohol dependence (AD; n = 65; males = 35, females = 30) to a group of BPO patients without comorbid AD (n = 61; males = 22, females = 39). The two groups were also similar on marital status and frequency of BPO subtypes. The results revealed that female bipolar alcoholic patients were more likely to report depressive symptoms as compared to either male bipolar alcoholics or both male and female non-alcoholic bipolar patients. When compared to male bipolar alcoholics, they had higher frequency of depressed mood, slow motor behavior, low self-esteem, decreased libido, decreased appetite, and higher general anxiety symptoms. On the other hand, female bipolar alcoholics differed from female non-alcoholic bipolar patients on reports of mood lability, depressed mood, low self-esteem, suicidal indicators, decreased libido, and general anxiety symptoms. These results raise the question of whether alcohol increases the frequency of depressive symptoms among female bipolar patients.

Treating the substance-abusing suicidal patient.

Studies concerning the treatment of substance-abusing suicidal patients are scarce despite the frequent presence of suicidal behavior among this population. Indeed, suicidality (ideation or behavior) is generally an exclusion criterion for participation in treatment studies of subjects with alcohol or drug abuse. Consequently, to date, little is known about the optimal treatment of this population. The first study involving substance-abusing suicidal patients was an open-label trial conducted in the early 1990s. This study involved 12 patients, all of whom demonstrated recent suicidal ideations and had made a lifetime suicide attempt. The results of that open-label study demonstrated significant within-group improvement in both depressive symptoms (including suicidal ideations) and level of drinking. However, substantial residual depressive symptoms and drinking persisted at the end of the trial. Also, because no placebo control group was utilized, the authors of that study could not rule out the possibility that the apparent therapeutic effect from fluoxetine was the result of the placebo effect. To date, only one double-blind, placebo-controlled study of subjects with alcohol or substance abuse has included substantial numbers of suicidal patients. The study involved 51 subjects, of whom 20 (39%) had made a suicide attempt in the current depressive episode, 31 (61%) had made a suicide attempt in their lifetime, and 46 (90%) had reported suicidal ideations in the week before hospitalization. The results of that double-blind, placebo-controlled study suggest that fluoxetine was effective in decreasing but not eliminating both the depressive symptoms (including suicidal ideations) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence, many of whom displayed suicidal ideations. A secondary data analysis from that study suggested that cigarette smoking is also significantly decreased by fluoxetine, but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone. Another secondary data analysis from that study suggested that marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust. A third secondary data analysis from that study suggested that cocaine abuse acts as a predictor of poor outcome for both depressive symptoms (including suicidality) and level of alcohol use in this population. The results of a 1-year naturalistic follow-up study involving the patients from that study suggest that the benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program. To date, no other double-blind, placebo-controlled studies involving substantial numbers of substance-abusing suicidal patients have been reported to either confirm or refute these findings. Further studies are clearly warranted to evaluate the efficacy of various pharmacotherapeutic agents and various psychotherapies in the treatment of substance-abusing suicidal patients.

Fluoxetine versus placebo in depressed alcoholics: a 1-year follow-up study.

The authors conducted a first study to evaluate the long-term efficacy of fluoxetine for decreasing the depressive symptoms and the drinking of patients with comorbid major depressive disorder and alcohol dependence. This study consisted of a 1-year naturalistic follow-up of 31 patients who previously had completed a 3-month double-blind, placebo-controlled study of fluoxetine in depressed alcoholics. The fluoxetine group continued to demonstrate less depressive symptoms and less drinking than the placebo group at the 1-year follow-up evaluation. The results of the 1-year follow-up evaluation suggest persistent efficacy for fluoxetine for treating the depressive symptoms and the drinking of depressed alcoholics.

Impact of substance abuse on the course and treatment of bipolar disorder.

OBJECTIVES: The objectives of this article are to review the prevalence, natural history, pathophysiology, and treatment of comorbid bipolar disorder with alcoholism and other psychoactive substance use disorders (PSUDs). METHODS: All identified bibliographies through a literature search of all Medline files and bibliographies of selected articles focusing on the prevalence, natural history, course, prognosis, inter-relationship, and treatment of bipolar disorder with comorbid alcoholism and other PSUDs were reviewed. RESULTS AND CONCLUSIONS: Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly prevalent. The presence of this so called 'dual diagnoses' creates a serious challenge in terms of establishing an accurate diagnosis and providing appropriate treatment interventions. The inter-relationship between these disorders appears to be mutually detrimental. The course, manifestation, and treatment of each condition are significantly compounded by the presence of the other condition. Substance abuse and alcoholism appear to significantly complicate the course and prognosis of bipolar disorder resulting in increased suffering, disability, and costs. On the other hand, bipolar disorder may be a risk factor for developing PSUDs. Although, there are a number of hypotheses explaining the pathophysiological mechanism involved in such comorbidities, our understanding of the exact nature of such neurobiological mechanisms is still limited. While the antikindling agents and targeted psychotherapeutic techniques may be useful intervention strategies, there is still a significant lack of empirically based treatment options for these patients.

Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study.

BACKGROUND: This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients. METHODS: Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month. RESULTS: Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed. CONCLUSION: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.

Fluoxetine versus placebo for the marijuana use of depressed alcoholics.

The aim of this analysis was to evaluate the efficacy of the SSRI antidepressant fluoxetine versus placebo for the marijuana use of depressed alcoholics. There are no previous reports involving and SSRI antidepressant for marijuana abuse. This analysis involved a subsample of 22 depressed alcoholic marijuana users out of a total of 51 depressed alcoholics. The entire sample was involved in a 12-week double-blind, placebo-controlled study evaluating the efficacy of fluoxetine versus placebo in depressed alcoholics. During the course of the trial, the cumulative number of marijuana cigarettes used was almost 20 times as high in the placebo group as in the fluoxetine group. Also, the number of days of marijuana use during the study was five times higher in the placebo group than in the fluoxetine group. These data suggest efficacy for fluoxetine in decreasing marijuana use of depressed alcoholics.

Increasing treatment adherence among outpatients with depression and cocaine dependence: results of a pilot study.

OBJECTIVE: This pilot study examined the effect of a modified motivational therapy intervention on outpatient treatment adherence and completion for patients with comorbid depressive disorder and cocaine dependence. METHOD: Depressed cocaine patients, stabilized with antidepressant medications on an inpatient psychiatric unit, were consecutively assigned on discharge to motivational therapy (N = 11) or treatment-as-usual (N = 12) during the first month of outpatient care. Patients were compared on treatment adherence and completion and on 1-year rehospitalization rates. RESULTS: Motivational therapy patients attended significantly more treatment sessions during month 1, completed 30 and 90 days of outpatient care at higher rates, and experienced fewer psychiatric rehospitalizations and days in the hospital during the first year from entry into outpatient treatment. CONCLUSIONS: An outpatient program combining individual and group motivational therapy sessions holds promise for improving treatment adherence and completion among depressed patients with cocaine dependence.

Scaling and root planing: hand versus power-driven instruments.

Scaling and root planing (S&RP) are regarded as the main modalities for treating periodontal disease. The goal of these treatments is to arrest the disease process, maintain a healthy periodontium and preserve the dentition. As prevention becomes a larger component of everyday dental practice, dentists are performing S&RP more often as part of their periodontal maintenance programs. Therefore, it is essential for dentists to know the latest S&RP techniques and methods. This paper reviews the current knowledge and experiences related to mechanical non-surgical periodontal therapy and focuses on the types of S&RP instruments that are available, their advantages and disadvantages, their efficacy in debridement, and their effects on the hard tissues of the oral cavity.

Naltrexone utility in depressed alcoholics.

The aim of this open-label pilot study was to evaluate the utility of naltrexone (50 mg per day) in decreasing alcohol use and to examine its impact on depressive symptoms among depressed alcoholics who have failed to abstain from alcohol use despite treatment with a selective serotonin reuptake inhibitor (SSRI). Fourteen ambulatory care patients, aged 18 to 65 years, with DSM-III-R comorbid diagnoses of alcohol dependence and major depressive disorder, who failed to abstain despite treatment with an antidepressant medication were enrolled in the study. Patients were followed for 12 weeks with weekly assessment of drinking behavior, depressive symptoms, functioning, alcohol craving, and side effects. The results of this study indicated a significant decrease in alcohol use and in urges to drink alcohol in the presence of the usual triggers. There was also a trend suggesting improvement in depressive symptoms and overall functioning. Naltrexone was well tolerated, with mild side effects reported at the onset of treatment.

Fluoxetine versus placebo in depressed alcoholic cocaine abusers.

To date, few double-blind, placebo-controlled studies with any selective serotonin reuptake inhibitor (SSRI) antidepressant in pure cocaine abusers or in cocaine abusers with comorbid disorders have been reported. In this study, 17 patients with DSM-III-R diagnoses of major depressive disorder, alcohol dependence, and cocaine abuse were included along with 34 non-cocaine-abusing depressed alcoholics in a pharmacotherapy trial involving the SSRI antidepressant fluoxetine. All 51 patients participated in a double-blind, parallel group study of fluoxetine versus placebo in depressed alcoholics. The principal focus of this article is the one-third of the depressed alcoholics who also abused cocaine and how the treatment response of those 17 patients compared with that of the 34 depressed alcoholics who did not abuse cocaine. During the study, no significant difference in treatment outcome was noted between the fluoxetine group (N = 8) and the placebo group (N = 9) for cocaine use, alcohol use, or depressive symptoms. In addition, no significant within-group improvement was noted for any of these outcome variables in either of the two treatment groups. Indeed, across the combined sample of 17 depressed alcoholic cocaine abusers, the mean Beck Depression Inventory (BDI) score worsened slightly from 19 to 21 during the course of the study, and 71 percent of the patients continued to complain of suicidal ideations at the end of the study. The 17 cocaine-abusing depressed alcoholics showed a significantly worse outcome than the 34 non-cocaine abusing depressed alcoholics on the 24-item Hamilton Rating Scale for Depression (HAM-D) and BDI depression scales and on multiple measures of alcohol consumption. These findings suggest that comorbid cocaine abuse acts as a robust predictor of poor outcome for the drinking and the depressive symptoms of depressed alcoholics.