Erythrocyte sodium pump activity in bipolar affective disorder and other psychiatric disorders

Erythrocyte ouabain-inhibitable sodium pump activity, a measure of NaK-ATPase activity, was studied in 6 diagnostic groups of psychiatric subjects: bipolar affective disorder, unipolar depressive disorder, neurotic depression, chronic alcohol abuse, schizoaffective disorder, and schizophrenia, and in sex- and age-matched normal controls. In the bipolar manic-depressive group, which was restricted to lithium-free subjects, values for sodium pump activity were significantly lower than in the controls (-11.4%, n = 53, p less than 0.001); subgrouping of the bipolar group by sex or age showed a significantly lower sodium pump activity in each of the groups. In the unipolar depressive group, values for sodium pump activity were significantly higher than in the controls (+13.7%, n = 12, p less than 0.01). The difference in direction of changed sodium pump activity between the bipolar and the unipolar groups was also observed in the values for subgroups of subjects in the two categories who were in a depressed state at the time the blood sample was taken. In the chronic alcohol abuse group, values for sodium pump activity were significantly higher than those for the control group (+13.5%, n = 20, p less than 0.05). In the neurotic depression (n = 24), schizoaffective (n = 12), and schizophrenia (n = 35) groups, there were no significant differences in sodium pump activity between the group of psychiatric subjects and their matched controls. These observations indicate that there is a trait-dependent deficiency of NaK-ATPase activity in bipolar affective disorder.     

Extended-release divalproex in child and adolescent outpatients with epilepsy

PURPOSE: To determine whether valproic acid [divalproex (DVP)] extended-release, administered at a higher proportionate once-daily dosage, can be safely substituted for delayed-release or sprinkle in pediatric patients with epilepsy. METHODS: Patients between ages 6 and 17 years with stable epilepsy taking DVP were randomized to 7 days of either DVP delayed-release/sprinkle (at the usual daily dose taken before study entry) or extended-release DVP (daily dose, 8% to 25% higher than their usual dose), and then (crossed over to) 7 days of the comparator formulation. Patient's clinical status was evaluated at a screening visit and on days 8 and 15, and with telephone follow-up 1 month after study completion. RESULTS: No statistically significant difference in mean plasma VPA levels measured at the end of treatment was observed: 99, 92, and 103 mug/ml with the delayed-release tablets (n = 4), the sprinkle formulation (n = 11), and the extended-release tablets (n = 16), respectively. Seizure-control rates were stable during patients' use of the extended-release formulation. None of the study patients experienced a treatment-related adverse event. CONCLUSIONS: The total daily dose for patients taking the delayed-formulation may need to be increased by < or = 20% when they are switched to the extended-release formulation. When switching from sprinkles to the extended-release formulation, individual variability must be considered. In patients who have VPA levels near the very high end of the therapeutic range (>100 microg/ml), it may be more prudent to make only minor modifications to the total daily dose during conversion and then to individualize the DVP extended-release dose based on plasma levels.     

Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: A comprehensive review

Deep transcranial magnetic stimulation (TMS) is a technique of neuromodulation and neurostimulation based on the principle of electromagnetic induction of an electric field in the brain. The coil (H-coil) used in deep TMS is able to modulate cortical excitability up to a maximum depth of 6 cm and is therefore able not only to modulate the activity of the cerebral cortex but also the activity of deeper neural circuits. Deep TMS is largely used for the treatment of drug-resistant major depressive disorder (MDD) and is being tested to treat a very wide range of neurological, psychiatric and medical conditions. The aim of this review is to illustrate the biophysical principles of deep TMS, to explain the pathophysiological basis for its utilization in each psychiatric disorder (major depression, autism, bipolar depression, auditory hallucinations, negative symptoms of schizophrenia), to summarize the results presented thus far in the international scientific literature regarding the use of deep TMS in psychiatry, its side effects and its effects on cognitive functions.     

Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review

The selective serotonin reuptake inhibitors (SSRIs) have emerged as a major therapeutic advance in psychopharmacology. As a result, the discovery of these agents marks a milestone in neuropsychopharmacology and rational drug design, and has launched a new era in psychotropic drug development. Prior to the SSRIs, all psychotropic medications were the result of chance observation. In an attempt to develop a SSRI, researchers discovered a number of nontricyclic agents with amine-uptake inhibitory properties, acting on both noradrenergic and serotonergic neurons with considerable differences in potency. A given drug may affect one or more sites over its clinically relevant dosing range and may produce multiple and different clinical effects. The enhanced safety profile includes a reduced likelihood of pharmacodynamically mediated adverse drug-drug interactions by avoiding affects on sites that are not essential to the intended outcome. SSRIs were developed for inhibition of the neuronal uptake pump for serotonin (5-HT), a property shared with the TCAs, but without affecting the other various neuroreceptors or fast sodium channels. The therapeutic mechanism of action of SSRIs involves alteration in the 5-HT system. The plethora of biological substrates, receptors and pathways for 5-HT are candidates to mediate not only the therapeutic actions of SSRIs, but also their side effects. A hypothesis to explain these immediate side effects is that 5-HT is increased at specific 5-HT receptor subtypes in discrete regions of the body where the relevant physiologic processes are regulated. Marked differences exist between the SSRIs with regard to effects on specific cytochrome P450 (CYP) enzymes, and thus the likelihood of clinically important pharmacokinetic drug-drug interactions. Although no clear relationship exists between the clinical efficacy, plasma concentration of SSRIs, nor any threshold that defines toxic concentrations, but therapeutic drug monitoring (TDM) may be useful in special populations, such as in elderly patients, poor metabolizers (PM) of sparteine (CYP2D6) or mephenytoin (CYP2C19), and patients with liver and kidney impairment. Several meta-analyses have reviewed the comparative efficacy of TCAs and SSRIs, and concluded that both TCAs and SSRIs have similar efficacy in the treatment of depression. SSRIs have demonstrated better efficacy and tolerability in the treatment of obsessive compulsive disorder (OCD). They have also been found to be effective in the treatment for social anxiety disorder both in reducing total levels of social anxiety and in improving overall clinical condition. The benefit of SSRIs in anorexia nervosa (AN) is apparently short-term unless medication is given in the context of nutritional or behavioral therapy. No single antidepressant can ever be recommended for every patient, but in a vast majority of patients, SSRIs should be considered as one of the first-line drugs in the treatment of depression.     

Alcoholism and other psychiatric disorders

Primary alcoholics may display symptoms of affective or psychotic disorders, while mentally ill patients may develop persistent alcohol-related problems. The author discusses the importance of distinguishing alcoholic psychosis from schizophrenia and alcohol-induced confusion from organic brain syndrome. He then outlines the diagnosis and treatment of other alcohol-induced conditions such as alcoholic dementia, antisocial behavior, and drug abuse. After stressing that primary alcoholism can mimic almost any psychiatric disorder, and secondary alcohol abuse can exacerbate any psychiatric symptoms, the author asserts that physicians should routinely include substance abuse as part of the differential diagnosis of psychiatric patients.     

Olfactory and gustatory functions in bipolar disorders: A systematic review

Olfactory and gustatory dysfunctions have been described in different psychiatric disorders. Several studies have found gustatory and olfactory function change in bipolar disorders with various results. The aim of this study is to have a systematic review of studies evaluating gustatory and olfactory function in bipolar disorders. After a systematic search, 15 studies on olfaction and 5 studies on taste were included in this review. The UPSIT (University of Pennsylvania Smell Identification Test) and Sniffin’ Sticks were the most widely used tests to evaluate smell. Some studies on olfaction described dysfunctions in smell identification as potential markers for bipolar disorders. Moreover, olfactory acuity was associated with psychosocial and cognitive performances. For taste, only few studies used standardized tests to evaluate gustation. These studies showed that patients with Bipolar disorders had more gustatory dysfunction compared to controls, and to non-bipolar depressed patients.     

Comorbidity: alcohol use and other psychiatric disorders

Alcohol related disorders often coexist with other psychiatric disorders and its incidence is increasing in last decades. Studies show that patients with comorbidity, specially those with severe psychiatric disorders, have higher rates of suicide, relapse, money spent in treatment, homeless and they use more medical service. Their evaluation must be meticulous because the differential diagnosis become complicated without a long period of alcohol withdrawal. These patients have a worse prognostic and their treatment is more difficult. Most of studies in this area have indicated that the integration of psychosocial and pharmacological techniques is more effective. The long term treatment must focus in the reduction of symptoms, improvement of social and familiar functioning, coping skills and relapse prevention.     

Separate and concomitant use of lamotrigine,lithium, and divalproex in bipolar disorders

Expert consensus emphasizes the need for better recognition and accurate diagnosis of bipolar disorder. Current research on lithium, divalproex, and lamotrigine provides new insight into the effective management of this illness. Advances in identifying the mechanism of action of mood stabilization has focused on signaling pathways within the cell that are associated with neurotrophic effects. Clinical research has led to confirmatory evidence of the efficacy of lithium in all phases of bipolar disorder, with the greatest effects seen in the treatment and prevention of mania. Compared to divalproex, lithium also has been found to have greater efficacy in the prevention of suicide. Lamotrigine has emerged as a first line treatment for bipolar depression, which is an area of weakness for other mood stabilizers. Oral loading of divalproex leads to rapid stabilization of mania without imposing a greater adverse effect burden than conventional dosing. Because no agent is universally effective in all phases of the illness, combination therapy with two or more agents often is the best option.     

How to differentiate bipolar disorder from attention deficit hyperactivity disorder and other common psychiatric disorders: A guide for clinicians

Bipolar disorder in children often is confused with attention deficit disorder, substance-induced mood disorder, oppositional defiant disorder, and conduct disorder. It is not uncommon for some of these disorders to be comorbid with pediatric bipolar disorder. This article provides the reader with a review of the existing literature on differentiating these illnesses and recognizing the phenomenology of each disorder as it pertains to a psychiatric diagnostic work-up of a child. Clinically helpful overlapping and unique characteristics of each disorder are discussed and a practical approach to differentiate these disorders is provided.     

How to differentiate bipolar disorder from attention deficit hyperactivity disorder and other common psychiatric disorders: A guide for clinicians

Bipolar disorder in children often is confused with attention deficit disorder, substance-induced mood disorder, oppositional defiant disorder, and conduct disorder. It is not uncommon for some of these disorders to be comorbid with pediatric bipolar disorder. This article provides the reader with a review of the existing literature on differentiating these illnesses and recognizing the phenomenology of each disorder as it pertains to a psychiatric diagnostic work-up of a child. Clinically helpful overlapping and unique characteristics of each disorder are discussed and a practical approach to differentiate these disorders is provided.     

Associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood: a community-based longitudinal investigation

OBJECTIVE: The study investigated cross-sectional and longitudinal associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood. METHOD: Psychiatric interviews were administered to a representative community sample of 717 youths and their mothers in 1983 (mean age of youths=14 years) and again in 1985-1986, and 1991-1993. RESULTS: A wide range of psychiatric disorders co-occurred with bipolar disorder during adolescence and early adulthood. Adolescent anxiety disorders were uniquely associated with increased risk for early adulthood bipolar disorder after adolescent bipolar disorder was accounted for. Manic symptoms during adolescence were associated with increased risk for anxiety and depressive disorders during early adulthood after adolescent anxiety and depressive disorders were accounted for. CONCLUSIONS: Adolescents with anxiety disorders may be at increased risk for bipolar disorder or clinically significant manic symptoms during early adulthood. Adolescents with manic symptoms may be at increased risk for anxiety and depressive disorders during early adulthood.     

Postpartum psychiatric disorders: a review

Postpartum emotional disorders generally fall into one of three categories: "blues," depressions, or psychoses. Such postpartum syndromes are described as to their presenting symptomatology, phenomenology, treatment, and prognosis. The role of the appropriate use of psychotropic medication in these conditions, after proper diagnosis, is also discussed. This overview is meant to be helpful to consultation-liaison psychiatrists and to other psychiatrists who work closely with obstetricians and primary care physicians.     

Anxiety disorders and bipolar disorder: a review

CONTEXT: Epidemiological, clinical and familial studies indicate that anxiety disorders (ADs) are highly comorbid in persons with bipolar disorder (BPD). The phenomenological overlap between ADs and BPD is reported more frequently in individuals with female predominant bipolar presentations (e.g., bipolar II disorder). Anxiety comorbidity in the BPD population poses a serious hazard. For example, it is associated with an intensification of symptoms, non-recovery, substance use comorbidity and harmful dysfunction (e.g., suicidality). OBJECTIVE: The evidentiary base informing treatment decisions for the anxious bipolar patient is woefully inadequate. Several expert consensus and evidence-based treatment guidelines for BPD suggest various treatment avenues, although these have been insufficiently studied. The encompassing aim of this paper is to synthesize extant studies reporting on the co-occurrence of AD and BPD. Taken together, a compelling basis emerges for prioritizing the identification and management of anxiety symptomatology in the BPD population.     

Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders.

BACKGROUND: The discovery of antidepressant medications has revolutionized the treatment of depression and other psychiatric illnesses. The coming of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) marked a new era in the treatment of depression. These therapies frequently fall short of getting the patient to remission. Agents with a dual action have subsequently been developed which inhibit the reuptake of both 5-HT and NE, getting more patients to remission. Physical symptoms are associated with depression, preventing the patient from obtaining complete recovery. This article provides an overview of the pharmacology, efficacy, and techniques for the clinical use of duloxetine, a dual reuptake inhibitor, which has recently become available. METHODS: The English literature has been reviewed including both controlled and uncontrolled studies. RESULTS: Duloxetine is a dual reuptake inhibitor with actions on serotonin as well as norepinephrine. It has been shown to have efficacy in treating depressive symptoms including those with painful physical symptoms. Common side effects include nausea, insomnia, and dizziness. CONCLUSIONS: The article has been written with clinicians as the target audience, the data suggesting it can be used as a first line agent.     

A review of herbal medicines for psychiatric disorders

OBJECTIVE: This review examines herbs commonly used for psychiatric symptoms-St. John's wort, kava, ginkgo biloba, and valerian. METHODS: MEDLINE was searched for articles related to the use of herbs in psychiatry published after 1990. A secondary search examined sources cited in articles obtained from the MEDLINE search. RESULTS: Of nine controlled and standardized trials of St. John's wort, five showed the herb's superiority to placebo, and four found no differences in effectiveness when compared with antidepressant drugs. The pharmacologically active components are not known. Several double-blind, placebo-controlled trials have demonstrated the anxiolytic efficacy of kava, but these studies had ill-defined patient populations, small sample sizes, and short treatment duration. All but one of 40 controlled trials of ginkgo extracts in the treatment of dementia found clinically significant improvement in memory loss, concentration, fatigue, anxiety, and depressed mood. Most studies of gingko had poorly defined patient populations and small sample sizes and used nonstandard measures. A recent well-designed multicenter study showed significantly less decline in cognitive function among patients with dementia receiving gingko. Valerian has been shown to decrease sleep latency and nocturnal awakenings and improve subjective sleep quality, but placebo effects were marked in some studies, and in some cases the beneficial effects were not seen until two to four weeks of therapy. CONCLUSIONS: Although evidence of the efficacy of herbal preparations in treating psychiatric conditions is growing, translating the results of efficacy studies into effective treatments for patients is hampered by the chemical complexity of the products, the lack of standardization of commonly available preparations, and the paucity of well-controlled studies.     

Pilot comparison of extended-release and standard preparations of divalproex sodium in patients with bipolar and schizoaffective disorders

OBJECTIVE: The authors compared the new extended-release and standard preparations of divalproex sodium. METHOD: Twelve patients with DSM-IV bipolar disorder or schizoaffective disorder who were clinically stable while taking the standard form of divalproex participated in the study. These patients were given a single daily dose of the extended-release preparation of divalproex in an open 6-week trial. Clinical symptoms and adverse effects were rated weekly. Doses were adjusted to maintain steady serum valproate concentrations. RESULTS: The medication change was associated with negligible changes in clinical status and tolerability. To maintain serum drug levels, however, 21% higher doses of the extended-release preparation were required. CONCLUSIONS: Use of extended-release divalproex once a day was as well tolerated as the standard preparation, with no change in efficacy within 6 weeks, but the daily dose needed to maintain stable serum valproic acid concentration was 21% higher.