Sixty young male patients with insomniac disorders were treated with nitrazepam 5 mg or triazolam 0.5 mg in a double-blind single night cross-over study. The results were favourable for triazolam in all the sleep parameters assessed. The significance of an hypnotic with a short life and its use in clinical practice is discussed.
In a double-blind, cross-over trial, triazolam (0.5 mg) was compared with nitrazepam (5 mg) in patients with disturbed sleep. Each drug was given once, with a 48-h interval, to 40 outpatients. Quality, duration, and latency of sleep, and number of awakenings during the night, showed a significant difference in favour of triazolam. An overall evaluation of sleep also showed triazolam to be superior to nitrazepam. Both drugs seemed to reduce dream activity and to alter the character of the dreams. There was no significant difference in side effects.
To examine the association between first hospital admissions due to postpartum psychosis and the explanatory variables age, educational level, marital status and year of delivery.
All Swedish first-time mothers (n = 502,767) were included during a 12-year period and followed for first hospital admissions due to postpartum psychosis. Cox regression was used to estimate hazard ratios, adjusted for the explanatory variables.
Older age and being a single mother implied an increased risk of first hospital admissions due to postpartum psychosis among first-time mothers. Educational level was not associated with first hospital admissions due to postpartum psychosis. During the 1990s, when a reduction in psychiatric beds occurred, first hospital admissions due to postpartum psychosis decreased significantly.
Certain sociodemographic factors are associated with first hospital admissions due to postpartum psychosis. Untreated postpartum psychosis due to fewer psychiatric beds could have hazardous effects on mothers and their children.
Zimelidine, a bicyclic compound, which in animal experiments causes specific inhibition of the uptake of 5-HT, was tried on 15 patients with depression of endogenous type. It produced considerable and highly significant 5-HT uptake inhibition in rat brain slices incubated in blood plasma from the patient under treatment, but no inhibition of NA uptake.
Depressive symptoms were effectively relieved or entirely abolished in about two thirds of the patients. Only four patients did not react to the drug, and three of these were probably in need of NA uptake inhibitors, which on other occasions had worked well on their depressions. These three patients showed an extreme degree of retardation. During zimelidine treatment they were not just unaffected but showed signs of excitation, impatience and desperate feelings. These preliminary findings strongly indicate the true existence of depressive cases in need of an NA uptake inhibitor, but completely resistant to a specific 5-HT uptake inhibitor.
The final dose of zimelidine was 75 mg b.i.d. This dose, although sufficient in most cases, was obviously somewhat low for a few of our patients. The concentration in blood plasma of zimelidine should probably reach a minimum level of 250 nmol/l and norzimelidine 500 nmol/l, and to achieve this a general dosage of 100 mg b.i.d. is recommended.
The severity of postpartum psychosis calls for further research on the association between obstetric variables and this psychiatric disorder.
A total of 1,133368 Swedish first-time mothers were included during a 29-year period yielding 1413 hospitalized cases of postpartum psychosis. Several obstetric variables were analysed separately after adjustment for possible confounders.
Respiratory disorder in the neonate, severe birth asphyxia, preterm birth, caesarean section, perinatal death and SGA infant were associated with an increased risk of postpartum psychosis. After adjustment for previous hospitalization for psychiatric disorder only preterm birth and acute caesarean section remained significant risk factors for postpartum psychosis (relative risks were 1.20 and 1.31 respectively). The relative risk of postpartum psychosis among first-time mothers with previous hospitalization for psychiatric disorder was increased more than 100-fold.
Careful clinical risk assessments of postpartum psychosis are crucial among women with a history of psychiatric disorder whereas obstetric variables have a minor importance.
To investigate seasonal and regional effects on bipolar I and II patients.
The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) patients were prospectively examined for monthly change in prevalence rates of depressed and recovered clinical status over the year. General Estimating Equation modeling was used to assess the effect of season on prevalence rates. Additionally, patients were stratified by bipolar subtype and by region.
A significantly higher prevalence rate of depression is observed in the northern sites, a significant prevalence by month effect is found only in the bipolar II patients.
The prevalence of depression is greater in patients from the northern vs. southern STEP-BD sites. Seasonal peak prevalence rates of depression differ by region. Bipolar II patients were more ill year-round and demonstrated greater monthly fluctuation in prevalence rates of being ill than did bipolar I patients. We conclude that seasonal effects upon bipolar patients vary by region and bipolar subtype.
Lifetime and 12-month prevalence of traumatic events and DSM-IV post-traumatic stress disorder as well as risk factors and comorbidity patterns were investigated in a representative community sample (n = 3021, aged 14-24 years).
Traumatic events and PTSD were assessed with the Munich Composite International Diagnostic Interview (CIDI).
Although 26% of male subjects and 17.7% of female subjects reported at least one traumatic event, only a few qualified for a full PTSD diagnosis (1% of males and 2.2% of females). Traumatic events and PTSD were strongly associated with all other mental disorders examined. PTSD occurred as both a primary and a secondary disorder.
The prevalence of PTSD in this young German sample is considerably lower than reported in previous US studies. However, the conditional probability for PTSD after experiencing traumas, risk factors and comorbidity patterns are quite similar. Traumatic events and full PTSD may increase the risk for other disorders, and vice versa.
We compared the prevalence and age of onset of adult and childhood anxiety disorders relative to the primary diagnosis in 68 women with anorexia nervosa (AN), 116 women with bulimia nervosa (BN), 56 women with major depression with no eating disorder (MD) and 98 randomly selected controls (RC) in order to determine whether antecedent anxiety disorders are plausible risk factors for AN and BN. Comorbid anxiety disorders were common in all three clinical groups (AN, 60%; BN, 57%; MD, 48%). In 90% of AN women, 94% of BN women and 71% of MD women, anxiety disorders preceded the current primary condition (P = 0.01), although panic disorder tended to develop after the onset of AN, BN or MD. In multivariate logistic regressions, the odds ratios (ORs) for overanxious disorder (OR = 13.4) and obsessive-compulsive disorder (OR = 11.8) were significantly elevated for AN. The ORs for overanxious disorder and social phobia were significantly elevated for BN (OROAD = 4.9; ORSP = 15.5) and MD (OROAD = 6.1; ORSP = 6.4). These data suggest that certain anxiety disorders are non-specific risk factors for later affective and eating disorders, and others may represent more specific antecedent risk factors.
To assess, in depressed patients, the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin.
In a 6-week double-blind study we compared the therapeutic efficiency and tolerance of mianserin 60 mg/day (N = 34), mianserin 60 mg/day plus fluoxetine 20 mg/day (N = 32) and continuing fluoxetine 20 mg/day (N = 38) in patients with major depression who did not respond to previous fluoxetine treatment.
Intent-to-treat analysis showed that at week 6 the decrease in the Hamilton Depression rating scale score was significantly (P < or = 0.03) greater in the mianserin plus fluoxetine group when compared to the fluoxetine group (effect size 0.665). Switching from fluoxetine to mianserin gave intermediate results. Mianserin augmentation of fluoxetine was well tolerated.
Mianserin augmentation of fluoxetine in patients non-responders to fluoxetine 20 mg/day increases response to treatment and is well tolerated.
Twelve hundred and six psychiatric in-patients, 506 men and 700 women, with severe depression/melancholia were rated at discharge with a multi-dimensional diagnostic schedule during 1956-1969. The sample was followed up until December 31, 1983. A total of 476 deaths were recorded including 103 suicides. Suicides and to a small proportion diseases of the nervous system constituted the total excess mortality in unipolar disorders. In bipolar disorders there was also an increased mortality from physical disorders, while the suicide frequency was lower (9% versus 4%). Male suicides had higher initial ratings for the items brittle, sensitive, marital problems, acute onset and lower ratings for psychomotor retardation than other men. Female suicides had a higher frequency of attempted suicides than other women. Acute onset and attempted suicide were associated with suicides early in the course contrary to the other differentiating items. The suicide frequency was similar in admissions during 1956-1962 compared with those during 1963-1969.
Objective:
Whether responses to antidepressants differ in bipolar and unipolar depression remains unresolved.
Method:
We analyzed patient characteristics and outcomes of antidepressant treatment of 1036 depressed patients with bipolar-I or bipolar-II disorder, or unipolar major depression, using bivariate and multivariate methods and survival analysis, testing the hypothesis that responses would be superior in unipolar depression.
Results:
Antidepressants were given to 84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117 bipolar-II, and 91.3% of 668 unipolar disorder cases. The 158 not given antidepressants had more manias/year, spent more months in mania and depression, and were far more likely to receive mood stabilizers or antipsychotics long term. Improvement of HDRS21 depression ratings ranked: bipolar-II (69.6%) > bipolar-I (62.9%) > unipolar (57.9%; P < 0.0001), independent of initial illness severity. Responder rates (≥50% improved without switching) ranked: bipolar-II (77.0%) > bipolar-I (71.6%) > unipolar (61.7%; P < 0.0001). Remission rates (final HDRS < 7) ranked: 54.0%, 50.6%, and 40.8% respectively (P = 0.02); 67.5% remitted within 12 weeks of treatment. Survival-computed median time to remission (15.0 weeks, overall) was shortest for bipolar-II patients (10.7 weeks). The 3-month risk of switching into mania-hypomania ranked: bipolar-II (15.8%) > bipolar-I (8.60%) > unipolar (0.56%). Multivariate modeling found bipolar diagnosis, shorter latency to remission, more recent trial year, and fewer weeks depressed before treatment to be associated with greater percent improvement of HDRS ratings.
Conclusion:
Selective use of antidepressants with or without mood stabilizers in non-agitated, depressed bipolar disorder patients for short periods was effective with moderate risk of potentially dangerous, manic mood elevation.
To provide a clinically useful analysis of the relationship between selective serotonin reuptake inhibitors (SSRIs), in particular fluoxetine and violent or suicidal behaviour.
All published papers on Medline and other databases linking serotonin, SSRIs and aggression were reviewed.
A small proportion of patients treated with SSRIs may become akathisic and others may show increases in anxiety in the initial phase of treatment, but no increased susceptibility to aggression or suicidality can be connected with fluoxetine or any other SSRI. In fact SSRI treatment may reduce aggression, probably due to positive effects on the serotonergic dysfunction that is implicated in aggressive behaviour directed towards oneself or others.
In the absence of convincing evidence to link SSRIs causally to violence and suicide, the recent lay media reports are potentially dangerous, unnecessarily increasing the concerns of depressed patients who are prescribed antidepressants.
Over recent years transcranial magnetic stimulation (TMS) has become widely applied in the study of neuropsychiatric disorders. The aim of this article is to review the application of TMS as an investigative tool and as a potential therapeutic modality in psychiatric disorders.
A comprehensive literature review.
When applied as an investigative tool, TMS provides innovative ways to directly study the excitability of the cortex, cortical regional connectivity, the plasticity of brain responses and cognitive functioning in illness and disease states. A number of studies suggest the potential of treatment with TMS in disease states, especially in patients with depression, although difficulties exist with the interpretation of the published literature.
TMS has a considerable role in neuropsychiatric research. It appears to have considerable potential as a therapeutic tool in depression, and perhaps a role in several other disorders, although widespread application requires larger trials and establishment of sustained response.
The relatively small number of male anorexia nervosa patients is often used as an excuse for the scarce literature on this subject. An exhaustive review of the literature (1970 to 1980), searching for case reports, yielded information about 107 males described as having anorexia nervosa. According to current criteria, the diagnosis was well documented in 37 patients. Data on the clinical picture and the social background were analysed and compared with a sample of 148 female anorectics. It was found that from the clinical point of view anorexia nervosa is strikingly similar in both sexes. A cluster analysis revealed that three subgroups might be distinguished in male cases: a '(pre)pubertal' variant, a 'lower class', and a 'middle class' variant. It is concluded that male patients should be involved in any future research on this syndrome.
To consider the impact of age and gender on the antidepressant response to nortriptyline and fluoxetine in melancholic depression.
Of 191 depressed patients, 113 met study criteria for melancholia. All patients were randomized to receive either fluoxetine or nortriptyline. Response rates, defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis, were examined by age, and by age and gender.
Melancholic depressed patients 40 years or older, especially men, had a markedly superior response to nortriptyline compared with fluoxetine. Conversely, melancholic depressed patients, age 18-24 years, especially women, had a markedly superior response to fluoxetine.
Age and gender appear to be critical variables in understanding differential antidepressant responses to tricyclic antidepressants and selective serotonin reuptake inhibitors in melancholic depression.
To investigate the rate of impulse control disorders among pathological gamblers and examine the relationship of comorbidity to gambling severity.
Ninety-six adult pathological gamblers [mean age: 46.7 +/- 11.0 years; female: 44 (45.8%)] completed the following: Minnesota Impulsive Disorders Interview, Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling, and Gambling Symptom Assessment Scale.
Twenty-two subjects (22.9%) reported a comorbid impulse control disorder, most commonly compulsive sexual behaviour and compulsive buying. Subjects with comorbidity reported significantly greater intensity of urges (t = -2.021; df = 94; P = 0.046) and thoughts (t = -2.147; df = 42.3; P = 0.038) related to gambling, and greater interference (t = -3.913; df = 48.1; P < 0.001) and distress (t = -2.504; df = 52.7; P = 0.015) secondary to gambling urges and thoughts.
Impulse control disorders appear common among pathological gamblers and are associated with more severe gambling symptoms.
In a cohort of subjects with no history of psychopathology, we determined a 3-year incidence and the risk factors of comorbid and pure mood, anxiety and substance use disorders.
Data were obtained from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a longitudinal community study in which 4796 adults were interviewed in 1996, 1997 and 1999 with the Composite International Diagnostic Interview.
Of 2869 cases at risk, 10.8% developed an incident disorder within 3 years, of which 16.1% was comorbid. Neuroticism, childhood trauma and parental psychiatric history were more strongly associated with comorbid than with pure disorders. No differences emerged in events occurring in the first year after baseline, but events in the period thereafter showed markedly stronger associations with comorbidity and pure mood disorder than with pure anxiety and substance use disorder. Functional disability was also linked more strongly to comorbidity and pure mood disorder.
Clear risk factors exist for the rapid onset of comorbidity. Interventions are needed to prevent rapid comorbidity in subjects who recently developed a primary disorder.
Objective:
This study sought to examine the age-dependent persistence of attention deficit hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood.
Method:
Participants were girls with (N=96) and without (N=91) ADHD and were 6-17 years old at the baseline assessment (mean age, 11 years) and 15-30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning.
Results:
At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning, and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline.
Conclusion:
These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier.
Japan was the first country to abandon the 19th century term of 'mind-splitting disease' (schizophrenia). Revisions of DSM and ICD are forthcoming. Should the rest of the world follow Japan's example?
A comprehensive literature search was carried out in order to review the scientific evidence for the validity, usefulness and acceptability of current concepts of psychotic disorder.
The discussion about re-classifying and renaming schizophrenia and other psychotic disorders is clouded by conceptual confusion. First, it is often misunderstood as a misguided attempt to change societal stigma instead of an attempt to change iatrogenic stigma occasioned by the use of misleading and mystifying terminology. Second, the debate is misunderstood as purely semantic, whereas in actual fact it is about the core concepts underlying psychiatric nosology. Third, it has been suggested that the debate is political. However, solid scientific evidence pointing to the absence of nosological validity of diagnostic categories lies at the heart of the argument. Fourth, there is confusion about what constitutes a syndrome (a group of symptom dimensions that cluster in different combinations in different people and for which one or more underlying diseases may or may not be found) and a disease (a nosologically valid entity with specific causes, symptoms, treatment and course).
Scientific evidence favours a syndromal system of classification combining categorical and dimensional representations of psychosis. The concept of 'salience' has the potential to make the public recognize psychosis as relating to an aspect of human mentation and experience that is universal. It is proposed to introduce, analogous to the functional-descriptive term 'Metabolic syndrome', the diagnosis of 'Salience syndrome' to replace all current diagnostic categories of psychotic disorders. Within Salience syndrome, three subcategories may be identified, based on scientific evidence of relatively valid and specific contrasts, named Salience syndrome with affective expression, Salience syndrome with developmental expression and Salience syndrome not otherwise specified.
Eleven beta-hydroxylase activity was assessed by measuring the cortisol to 11-deoxycortisol ratio in 20 control subjects, 38 patients with major depression, and five patients with Cushing's disease before and after 1 mg of dexamethasone. The mean levels of 11 beta-hydroxylase activity did not differ among groups before dexamethasone. After dexamethasone patients with Cushing's disease showed a nonsignificant increase in 11 beta-hydroxylase activity while patients with major depression and controls subjects both showed a decrease. Endogenous depressive patients were no more likely to show high 11 beta-hydroxylase activity than neurotic depressive patients; however, depressed patients with cortisol nonsuppression after dexamethasone were. Post-dexamethasone 11 beta-hydroxylase activity is positively correlated with age in both control subjects and patients with depression.
The dexamethasone suppression test based upon analysis of 11-deoxycorticosterone, corticosterone and cortisol was applied to 20 female depressed patients (10 endogenous, 10 neurotic) and 10 healthy controls. Calculating ratios of corticosterone to its biological precursor 11-deoxycorticosterone allows to assess the activity of adrenal 11 beta-hydroxylase. This enzyme activity depends on the mean secretion rate of ACTH. The preliminary data indicate that the sensitivity of the test may be increased when based on this enzyme activity rather than upon plasma cortisol concentrations. The decrease of 11-deoxycorticosterone, a potent mineralocorticoid in relation to corticosterone may contribute to the reduced urine concentrating capacity in patients with endogenous depression.
Objective:
For psychiatric diagnoses, solving the problem of false positives is thought to be a matter of tightening diagnostic criteria. But low prevalence illnesses by their nature have high false positive rates. A recent study of bipolar disorder found the predictive value of bipolar diagnoses to be <50%. Is it possible to achieve much higher diagnostic accuracy for psychiatric diagnoses?
Method:
We calculate predictive values while varying diagnostic sensitivity and holding specificity constant, and vice versa, for a given prevalence of illness. We then calculate predictive values while holding sensitivity and specificity constant, but varying prior probability (clinically feasible by assessing other factors associated with bipolar outcomes, such as family history and degree of recurrence).
Results:
Assuming a sample in which the prevalence of illness is 10%, achieving positive predictive values (PPV) >50% requires diagnostic specificity of >95%. Holding specificity at a level already achieved clinically (86%), increasing prior probability yields predictive values as high as 83%.
Conclusion:
Systematic assessment of clinical factors that increase the prior probability of illness, before applying DSM/ICD criteria, could raise PPV substantially compared with targeting greater specificity via more stringent diagnostic criteria.
