Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial.

Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day(-1) (up to 40 mg day(-1)) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were -3.04 (95% CI -6.95, 0.86) and -2.4 (95% CI -6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression.

Homeopathic Individualized Q-potencies versus Fluoxetine for Moderate to Severe Depression: Double-blind, Randomized Non-inferiority Trial

Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day(-1) (up to 40 mg day(-1)) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Asberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates [...] Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were -3.04 (95% CI -6.95, 0.86) and -2.4 (95% CI -6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression.(AU)

Family interventions for bipolar disorder.

BACKGROUND: Pharmacological treatments are the principal intervention for bipolar disorder. Alone, however, they are not sufficient to control symptoms and maintain psychosocial functioning. Adjunctive psychosocial interventions may help to improve the patient's condition and the course of the illness. Family interventions are deserving of special attention, since they may help to relieve the burden of care borne by relatives and caregivers, which in turn may facilitate the task of supporting the patient. OBJECTIVES: The objective of this review was to investigate the effectiveness of family interventions in the treatment of bipolar disorder compared with no intervention and other forms of intervention. SEARCH STRATEGY: We searched the electronic databases CCDANRCT-Studies and CCDANCTR-References on 1/8/2007, CENTRAL (2006-3), MEDLINE (2006), EMBASE (2006) and LILACS (2006), and searched the reference lists of included studies. We also made personal contact with authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised trials. Participants were people with bipolar disorder and their relatives or caregivers; family psychosocial interventions of any type were considered; primary outcomes were changes in the status of symptoms and relapse rates. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two review authors. Quality assessment of included studies was carried out. The findings were presented descriptively. Where there were sufficient studies, dichotomous data were combined using relative risk, and continuous data were combined using weighted mean difference, with their 95% CIs. MAIN RESULTS: Seven RCTs were included in the review, involving a total of 393 participants. All of the included studies assessed psychoeducational methods, and one study also assessed a type of systems psychotherapy. In all trials, participants continued to receive pharmacotherapy treatment. Due to the diversity of interventions, outcome measures and endpoints used across studies, it was not possible to perform meta-analyses for primary outcomes. Five studies compared a variety of family interventions, involving carers, families or spouses, against no intervention, with individual findings indicating no significant added effect for family interventions. Three studies compared one type or modality of family intervention against another family intervention, with inconsistent findings. AUTHORS' CONCLUSIONS: To date there is only a small and heterogeneous body of evidence on the effectiveness of family oriented approaches for bipolar disorder, and it is not yet possible to draw any definite conclusions to support their use as an adjunctive treatment for bipolar disorder. Further well designed RCTs should be a research priority.

Acute effects of low doses of melatonin on the sleep of young healthy subjects.

This study was undertaken to evaluate the acute effects of single low doses of melatonin given to healthy volunteers in the evening. Six healthy male volunteers (age range 22-24 years) participated in this study, after signing an informed consent form. They received in a double-blind fashion placebo or 0.3 or 1.0 mg melatonin at three fixed times: 18:00, 20:00, and 21:00 hr. Polysomnographic recordings began immediately thereafter, with their being allowed to sleep. Prior to each experimental session and in the following morning, subjects completed a sleep quality questionnaire, the Profile of Mood States, the Stanford Sleepiness Scale, and underwent a visual reaction test. Significant decrease on sleep latencies was found following melatonin treatment at 18:00 and 20:00 hr. In addition, melatonin tended to improve sleep efficiency and to reduce intermittent wakefulness. However, at 21:00 hr, 0.3 mg melatonin increased latency to sleep onset and 1.0 mg melatonin had no effect on sleep variables. Furthermore, melatonin given at different times did not alter subjective sleepiness, mood, and reaction time in the following morning. The results from the present study support the notion that administration of low doses of melatonin, mimicking the nocturnal physiological concentration of this hormone may exert immediate sleep-inducing effects.

Fluoxetine: a suitable long-term treatment.

A review of fluoxetine's safety profile, especially during long-term treatment, is presented. Key safety advantages for fluoxetine include lower adverse events and dropout rates compared with tricyclic antidepressants and other selective serotonin reuptake inhibitors (SSRIs), safety in overdose, and safe use in special population groups such as women in pregnancy. Prospectively ascertained pregnancy outcomes following exposure to SSRIs, mainly fluoxetine, consistently show no teratogenic effects as assessed in the postnatal period and in comparison with controls. An additional advantage of fluoxetine is the absence or mildness of discontinuation symptoms following treatment interruption, probably a consequence of fluoxetine's long half-life in comparison with other SSRIs. The available data on these topics confirm the suitability of long-term fluoxetine treatment.

Clinical utility of the premenstrual assessment form as an instrument auxiliary to the diagnosis of premenstrual dysphoric disorder.

The Premenstrual Assessment Form (PAF) is a retrospective self-report questionnaire, yielding classification into syndromal categories and severity assessment (unipolar summary scales) of behavioral, psychological and physical premenstrual changes. However, the PAF has been criticized due to an overlap of its syndromal categories and the unipolar summary scores from symptomatic and asymptomatic women. PAF data from women seeking treatment for premenstrual symptoms and meeting a provisional diagnosis of premenstrual dysphoric disorder (PMDD; n=30) were compared to a control group (n=16). Results showed that 97% of the symptomatic group met the PAF depressive premenstrual syndrome criteria vs. only 12% of the control subjects (chi(2)=29.9, P<0.001). The symptomatic group also reported more severe premenstrual symptoms in all unipolar scales than the control subjects. Sixteen symptomatic women completed two menstrual cycles of prospective daily ratings, and half of them had their provisional diagnosis of PMDD confirmed. There were no significant differences in the scores of the PAF unipolar summary scales between the subgroups with or without the diagnosis confirmation. Most of the PAF scales displayed high sensitivity, but low specificity. These findings suggest that the PAF can be useful to differentiate clinical population and control samples, but it does not provide information to make a more definite diagnosis of PMDD.

MK-801 blocks the development of behavioral sensitization to the ethanol.

BACKGROUND: Studies have indicated that MK-801 (a noncompetitive N-methyl-D-aspartate receptor antagonist) participates in the long-term neural changes responsible for sensitization to stimulant drugs. It is known that repeated administration of low doses of ethanol sensitizes animals to its stimulant effect. In this work we investigated whether MK-801 alters the development of behavioral sensitization to ethanol. METHODS: Groups of male Swiss mice were treated with saline or ethanol (2.0 g/kg) plus saline or MK-801 (0.25 mg/kg) for 21 days. On day 25, all animals received an ethanol challenge injection (2.0 g/kg). We measured locomotor activity on days 1, 7, 14, 21) and 25. In addition, we assessed the effects of different doses of MK-801 on the response to a low dose of ethanol (2.0 g/kg). RESULTS: Ethanol-treated mice developed sensitization to the locomotor-stimulating effect of the drug, whereas those concomitantly receiving ethanol and MK-801 did not. All doses of MK-801 that were used stimulated the locomotor activity of both ethanol and saline-treated animals. CONCLUSIONS: The findings support the hypothesis that N-methyl-D-aspartate receptors have an important role in the development of sensitization to drugs of abuse.

Affective disorders, hospital admissions, and seasonal variation of mania in a subtropical area, southern hemisphere.

Hospital admissions (n = 15,450) to a state psychiatric hospital in Botucatu, São Paulo State, Brazil, over a 10-year period (1982-1991) were reviewed. 157 (1%) patients received a probable diagnosis of affective disorder according to DSM-III-R criteria. Among them, 46% had been diagnosed by the staff psychiatrists, and their diagnoses were sustained by the researchers, whereas 54% were diagnosed only by one of the researchers (F.K.C.). These last patients had previously received a diagnosis of paranoid schizophrenia or unspecified psychosis (ICD-9). Most of the patients with affective disorders were bipolar: 72 and 8%, respectively, presented manic and depressive episodes. Thus, only 20% received a diagnosis of major depression. A seasonal pattern in hospital admission was observed only for mania in women, their episodes occurring more often (p < 0.02) in spring and summer. No significant seasonal pattern in hospital admission for depression was found.

Moclobemide effects on prolactin plasma levels in healthy individuals: the hormonal increase induced by a single dose is maintained during a 4-week period of drug intake.

Neuroendocrine challenge studies are frequently used to study the pathophysiology of psychiatric illnesses and the effects of psychotropic drug treatment on brain monoamine function. Moclobemide, a reversible inhibitor of monoamine oxidase, with predominant effects on the A-type of the enzyme, was administered to 15 healthy men. Seven out of the 15 also received single blind placebo a week before the moclobemide. The individuals received moclobemide as a single dose (150 mg), followed by doses of 150 mg three times a day, during a 4-week period. Plasma prolactin was measured in the morning over a 150-min period, following the single dose, and then at the end of weeks 1, 2 and 4 of moclobemide intake. The present data show an acute and transitory increase of plasma prolactin levels after the single dose, and also during the long-term moclobemide administration. It might indicate that steady-state moclobemide levels, during the long-term drug administration, were low and thus large fluctuations of drug levels occurred between doses. Thus, it is suggested that larger doses or administering smaller doses more frequently, or both, may induce hyperprolactinaemia with clinical consequences.

Avaliacao da eficacia, tolerabilidade e seguranca da sertralina (50 mg a 200 mg) durante 8 semanas no tratamento de 150 pacientes ambulatoriais com depressao maior

Os resultados de um estudo multicentrico, aberto e nao comparativo, no qual foram avaliados 150 pacientes com diagnostico de depressao maior de acordo com os criterios do DSM-III-R, sao relatados. Os pacientes selecionados foram inicialmente submetidos a um periodo simples-cego de placebo, durante 2 semanas. Apos essa fase, aqueles que preenchiam os criterios de inclusao e exclusao iniciaram o tratamento com sertralina 50 mg/dia que poderia ser aumentada gradualmente ate 200 mg/dia, em incrementos de 50 mg, e intervalos de no minimo 2 semanas, caso a resposta ao tratamento fosse insatisfatoria, segundo a avaliacao do investigador. O tratamento com sertralina mostrou-se altamente eficaz no alivio da depressao, como tambem nos sintomas associados ao quadro depressivo como, ansiedade, transtornos do sono, agitacao ou inibicao psicomotora, trabalho e atividades, entre outras. Um total de 84,2 por cento dos pacientes responderam satisfatoriamente ao tratamento com sertralina em doses flexiveis. Em relacao a tolerabilidade, um total de 54 por cento dos pacientes apresentaram algum efeito adverso ao longo do tratamento, porem estes efeitos foram geralmente de intensidade leve ou moderada e apenas 4,6 por cento dos pacientes interromperam o tratamento premeturamente devido a ocorrencia de eventos adversos.

WHO Neuropsychiatric AIDS study, cross-sectional phase I. Study design and psychiatric findings.

BACKGROUND: Most available studies on the psychiatric, neuropsychological, and neurological complications of HIV-1 infection and AIDS have been conducted in Western countries, on samples of well-educated, mostly white, homosexual men. Concerns about generalizability of the results of those investigations prompted the WHO to implement the cross-cultural venture called WHO Neuropsychiatric AIDS study. METHODS: This project aims to assess the prevalence and natural history of HIV-1-associated psychiatric, neuropsychological, and neurological abnormalities in representative subject samples enrolled in the five geographic areas predominantly affected by the HIV-1 epidemic. Assessment is made by a data collection instrument including six modules. The intercenter and intracenter reliability in the use of each module has been formally evaluated. The study consists of a cross-sectional phase and a longitudinal follow-up. RESULTS: The cross-sectional phase was completed in five centers. This paper reports on the results of psychiatric assessment, which revealed a significantly higher prevalence of current mental disorders in symptomatic seropositive persons compared with seronegative controls among intravenous drug users in Bangkok and homosexuals/bisexuals in São Paulo. The mean global score on the Montgomery-Asberg Depression Rating Scale was significantly higher in symptomatic seropositive individuals than in matched seronegative controls in all centers. CONCLUSIONS: These results suggest that the significance of the psychopathological complications of symptomatic HIV-1 infection may have been underestimated by previous studies conducted on self-selected samples of well-educated, middle-class, mostly white, homosexual men.

The effects of lithium carbonate on healthy volunteers: mood stabilization?

A 2-month lithium-placebo double-blind cross-over study was carried out with 17 healthy volunteers. Their mood was self-rated: twice daily (AM, PM) with the Visual Analogue Mood Scale (VAMS); weekly with the analogue scales for subjective states and body symptoms; and three times (basal and at the end of each treatment period) with the Profile of Mood States (POMS). Memory and reaction time were also assessed, but did not show any change. The mean VAMS score decreased during lithium treatment, but the mean mood variability, a measure of the mean successive differences between consecutive mood ratings (delta squared), did not change significantly. There was a tendency toward decreased mood variability on lithium, both during the full 1-month treatment period and in the last week of treatment, when all volunteers had a lithium serum level ranging from 0.6 to 1.0 mEq/liter. The lower mean VAMS scores on lithium could be attributed to lithium-induced dysphoric mood as recorded on the analogue scales and POMS. However, very large inter- and intraindividual differences in response to lithium were observed. Actually, lithium even had an opposite effect on some volunteers' mood. The data and problems involved with assessment of mood and its changes are discussed.

The dexamethasone suppression test: its relationship to diagnoses, severity of depression and response to treatment.

1. The dexamethasone suppression test (DST) was applied to 40 depressed patients, 40 healthy volunteers and 40 patients with other psychiatric disorders. 2. The post-dexamethasone cortisol level, adopted as the non-suppression criterion and established locally, was 3.0 micrograms/dl. 3. The DST sensitivity in depression was 45%, with a specificity of 95% and a positive predictive value of 90%. 4. There was a significant correlation (r = 0.38, p less than 0.05) between HDRS scores of depressed patients and their post-dexamethasone cortisol levels. 5. A prospective study of the depressed group, which was assessed with three depression rating scales, showed differences between non-suppressors and suppressors regarding to the symptoms severity and response to the treatment. It suggests that an abnormal DST result could have a prognostic value to antidepressant drugs and ECT. 6. The DST specificity in depression was also calculated from its performance in the group with other psychiatric disorders, and their diagnoses as well as the abnormal DST results were critically discussed.

Effects of desipramine and total sleep deprivation on hormonal levels of healthy subjects.

Plasma prolactin (PRL) and growth hormone (GH) were serially measured over a 5-hour morning period in healthy subjects who twice received a single oral dose of 100 mg desipramine (DMI). The study was carried out both after a regular night of sleep and after 1 night of total sleep deprivation. Clinical studies have suggested that sleep deprivation could potentiate the therapeutic effects of antidepressants, and there were reports on DMI stimulation of GH. The basal PRL levels decreased after sleep deprivation, but subsequently increased after DMI, whereas the same dose of DMI did not affect PRL in the absence of after DMI, whereas the same dose of DMI did not affect PRL in the absence of sleep deprivation. The GH levels increased substantially (8- to 10-fold) after DMI in both experimental conditions. Sleep deprivation neither changed GH basal levels nor potentiated the DMI-induced GH increase.

Depression assessment in Brazil. The first application of the Montgomery-Asberg Depression Rating Scale.

Cross-cultural investigation in psychiatry is revealing the need for standardised instruments in diagnosing and assessing depression. Recently, a new instrument was developed to evaluate depressed patients, namely the Montgomery-Asberg Depression Rating Scale (MADRS). The present study introduced the MADRS in Brazil, comparing it to the Hamilton Depression Rating Scale, the Visual Analogue Mood Scale (a self-rating scale), and with the global clinical assessment of independent Brazilian psychiatrists. The results show correlation between MADRS and the three other assessments, indicating that it is a useful and operational instrument to evaluate depressed patients. They also support the application of the MADRS in cross-cultural studies of depression in Brazil and other countries. These results are critically discussed.

Pharmacology of lemongrass (Cymbopogon citratus Stapf). III. Assessment of eventual toxic, hypnotic and anxiolytic effects on humans.

A herbal tea (called an abafado in Brazil) prepared from the dried leaves of lemongrass was administered to healthy volunteers. Following a single dose or 2 weeks of daily oral administration, the abafado produced no changes in serum glucose, urea, creatinine, cholesterol, triglycerides, lipids, total bilirubin, indirect bilirubin, GOT, GPT, alkaline phosphatase, total protein, albumin, LDH and CPK. Urine analysis (proteins, glucose, ketones, bilirubins, occult blood and urobilinogen) as well as EEG and EKG showed no abnormalities. There were slight elevations of direct bilirubin and of amylase in some of the volunteers, but without any clinical manifestation. These results taken together indicate that lemongrass as used in Brazilian folk medicine is not toxic for humans. The eventual hypnotic effect of lemongrass was investigated in 50 volunteers who ingested samples of lemongrass and a placebo under double-blind conditions. The parameters (i.e. sleep induction, sleep quality, dream recall and rewakening) did not show any effect of lemongrass as compared to the placebo. Eighteen subjects with high scores of trait-anxiety were submitted to an anxiety-inducing test following taking lemongrass or placebo under double-blind conditions. Their anxiety levels were similar, indicating that the abafado of the plant does not have anxiolytic properties. It is concluded that lemongrass, one of the most popular Brazilian herbal medicines, used for its alleged CNS-depressant effects, is atoxic but lacks hypnotic or anxiolytic properties.

The effects of REM sleep deprivation on striatal dopamine receptor sites.

3H-Spiroperidol binding to dopamine receptor sites of rat striatal tissue was studied following 24, 48, 72 and 96 hr of rapid eye movement sleep deprivation (REM dep.). The density of dopamine receptor binding sites (Bmax) was decreased after 48, 72, and 96 hr of REM dep. The apparent dissociation constant (KD) decreased after 96 hr, indicating an increase in apparent affinities. The control experimental animals also presented a time-dependent decrease of Bmax and KD as compared to unhandled controls. These results suggest that dopaminergic mechanisms may indeed be involved in the effects of REM sleep deprivation and/or stress.

Selective antidepressants and cerebrospinal fluid. Lack of specificity on norepinephrine and serotonin metabolites.

Cerebrospinal fluid concentrations of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid, were measured in depressed patients before and after treatment with three putatively specific antidepressants. The expected specificity of action on these three neurotransmitter metabolites was not observed. Desipramine hydrochloride, a norepinephrine uptake inhibitor, reduced 5-HIAA as well as MHPG concentrations; zimeldine hydrochloride, a serotonin uptake inhibitor, reduced MHPG as well as 5-HIAA concentrations; and clorgyline, a selective monoamine oxidase type A inhibitor, which might be predicted to most affect 5-HIAA, dramatically reduced MHPG, moderately reduced homovanillic acid, and only modestly reduced 5-HIAA concentrations.

Chronic lithium prevents REM sleep deprivation-induced increased responsiveness to apomorphine.

REM sleep deprivation of rats induces an increased responsiveness to dopaminergic agonists. Chronic lithium (Li) has been reported to prevent the development of dopamine receptor supersensitivity induced by other agents. The effects of chronic dietary Li administration (producing a mean serum level of 0.96 mequiv. litre-1) and 96 h REM sleep deprivation were studied. Chronic Li completely blocked the increased stereotypy, and partially prevented the aggressive behaviour induced, respectively, by 0.6 and 5 mg kg-1 of apomorphine in REM sleep deprived rats compared with the appropriate control groups. This study constitutes the first attempt to evaluate chronic lithium effects on rats undergoing REM sleep deprivation, chosen as another method of inducing alteration of dopaminergic sensitivity.