Trevor Silverstone

Appetite suppressants : a review

SummaryCentrally acting appetite suppressant drugs used in the treatment of obesity fall into 2 broad pharmacological categories; those which act via brain catecholamine pathways and those which act via serotonin pathways. Of the former group, amphetamine and phenmetrazine are no longer recommended because of their stimulant properties and addictive potential. The remaining drugs in this class include amfepramone (diethylpropion), phentermine, mazindol and phenylpropanolamine. All have been shown to reduce appetite and lower food intake, thereby helping obese patients more easily keep to a low-calorie diet and lose weight. They all have some sympatho-mimetic and stimulant properties. Anorectic drugs which promote serotonin neurotransmission have no such stimulant or sympathomimetic properties. They are fenfluramine, together with its recently introduced dextrorotatory stereoisomer dexfenfluramine, and fluoxetine. They reduce appetite and food intake and are effective in the treatment of obesity.Anorectic drugs should be reserved for those who are clinically at risk from being overweight, and then only as part of a comprehensive weight-reducing programme including regular dietary counselling. Although current licensing regulations only allow their use over a relatively short period (12 to 16 weeks), clinical trials have shown them to be effective over longer periods, particularly in preventing weight regain. Of the compounds currently indicated for use in obesity, dexfenfluramine appears to have the most suitable pharmacological profile, although it should not be given to patients with a history of depression.When used appropriately, appetite suppressants can be of real therapeutic benefit, and pose little risk.

Serotonin and bipolar disorder

With the emergence of specific pharmacological probes for various serotonin (5-HT) receptors and radio-ligands for central 5-HT, it has now become possible to investigate its role in the pathogenesis of bipolar disorder more closely. This paper critically reviews the scientific literature regarding the relationship between bipolar disorder and serotonergic systems. The evidence suggests that central serotonergic activity is reduced in the depressive phase of bipolar disorder. Similar findings have been reported in bipolar patients when euthymic, indicating that that lower 5-HT activity could be a trait marker for bipolar disorder. Findings reported in the manic phase of this illness are inconsistent.

Gender differences in the symptoms of major depressive disorder.

Data from the Canadian Community Health Survey 1.2 were used for a gender analysis of individual symptoms and overall rates of depression in the preceding 12 months. Major depressive disorder was assessed using the Composite International Diagnostic Interview in this national, cross-sectional survey. The female to male ratio of major depressive disorder prevalence was 1.64:1, with n = 1766 having experienced depression (men 668, women 1098). Women reported statistically more depressive symptoms than men (p < 0.001). Depressed women were more likely to report “increased appetite” (15.5% vs. 10.7%), being “often in tears” (82.6% vs. 44.0%), “loss of interest” (86.9% vs. 81.1%), and “thoughts of death” (70.3% vs. 63.4%). No significant gender differences were found for the remaining symptoms. The data are interpreted against womens greater tendency to cry and to restrict food intake when not depressed. The question is raised whether these items preferentially bias assessment of gender differences in depression, particularly in nonclinic samples.

Prevalence of migraine in bipolar disorder

BACKGROUND This study was undertaken to estimate the prevalence of migraine in people suffering from bipolar affective disorder. METHODS a headache questionnaire incorporating the newly introduced International Headache Society (IHS) criteria was given to 117 patients on the Dunedin Bipolar Research Register. RESULTS a total of 81 (69%) completed the questionnaire, out of which 21 (25.9%) reported migraine headaches. 25% of bipolar men and 27% of bipolar women suffered from migraine. CONCLUSIONS these rates are higher than those reported in the general population with the rate for bipolar men being almost five-times higher than expected. An increased risk of suffering form migraine was particularly noted in bipolar patients with an early onset of the disorder. This may represent a more severe form of bipolar affective disorder.

Dopamine in manic depressive illness ☆: A pharmacological synthesis

If the clinical symptoms of mania are a consequence of increased activity in central dopaminergic (DA) pathways in predisposed individuals, then drugs increasing DA neurotransmission should precipitate or exacerbate mania in such people, whereas drugs which reduce DA neurotransmission should ameliorate manic symptoms. Of the drugs which enhance DA neurotransmission, those which increase synthesis of DA (levodopa), those which promote DA release (amphetamine), and those which act directly as agonists or DA receptors (bromocriptine) have all been shown to precipitate mania. Conversely, drugs which reduce DA neurotransmission by inhibiting synthesis (alpha-methylparatyrosine) or by blocking DA receptors (pimozide) are effective in reducing manic symptoms. DA systems are not working in isolation; evidence is presented showing an influence on manic illness of central cholinergic and GABA-ergic processes. It is suggested that there is an interacting set of neurotransmitter pathways linking the limbic system and the ventral tegmental (A10) area involving DA, acetylcholine and GABA upon which drugs can act to influence the course of a manic illness.

A review of acute treatments for bipolar depression.

Bipolar patients generally spend much more time in the depressed phase of their illness than the manic phase, and there are many more bipolar type II and bipolar spectrum disorder patients than there are bipolar type I. Additionally, there is a significant risk of suicide in bipolar patients when depressed. The treatment of the depressed phase of bipolar disorder is therefore a matter of some priority. Here, we review current evidence supporting the use of five groups of treatments: anti-depressants; lithium; anti-convulsants (valproate, and carbamazepine, lamotrigine, gabapentin); anti-psychotics; and other treatments (electroconvulsive therapy, benzodiazepines, sleep-deprivation, and dopamine agonists). From this review, it is apparent that the literature regarding the treatment of bipolar depression is significantly limited in several key areas. Nonetheless, from the evidence currently available, the treatments with the best evidence for efficacy are selective serotonin reuptake inhibitors (SSRIs) and lamotrigine. There is also some evidence in favour of bupropion and moclobemide. Although lithium and olanzapine monotherapies can also be beneficial, they appear less efficacious than antidepressants. One of the major concerns about treatment with antidepressants has been the risk of precipitating a switch into mania. However, recent studies suggest that, if a mood stabilizer and antidepressant are given concurrently, then the risk of switching is minimized. There is also recent evidence for an independent antidepressant action for at least one atypical antipsychotic. Therefore, the conclusion from this review, in contrast to previous suggestions, is that a combination of an atypical antipsychotic and either an SSRI or lamotrigine may provide a useful first-line treatment for depressed bipolar disorder patients. Further research is clearly required to examine this approach and compare it with other possible treatment options.

Long Term Treatment of Bipolar Disorder

SummaryBipolar disorder is characterised by recurrent episodes of mania and depression. The major objective of long term treatment is to reduce the frequency of these episodes. Lithium is the most widely recommended drug for this purpose, having been shown in controlled clinical trials to be more effective than placebo in reducing the likelihood of relapse. Unfortunately, its effectiveness in clinical practice is less than that predicted from these trials. A major cause of relapse is noncompliance, largely due to intolerance to adverse effects such as perceived mental sluggishness, thirst, polyuria and weight gain. Regular monitoring of lithium plasma concentrations is required to ensure that the range of 0.5 to 0.9 mmol/L is not exceeded. Concentrations above this can lead to toxic symptoms, which if unchecked can cause brain damage and even death.The anticonvulsant drugs carbamazepine and valproic acid (sodium valproate) are potential alternatives to lithium. Patients who relapse frequently despite lithium may benefit from the addition of one of these agents, although formal clinical trial evidence of the efficacy of such combination treatment is lacking. Antipsychotics, administered as a depot formulation, can reduce the likelihood of relapse in patients with frequent manic episodes, especially if associated with poor compliance. Psychological treatment and patient education have been shown to improve outcome, and should be made more widely available to all patients with bipolar disorder.

Familial Bipolar Disorder: Preliminary Results from the Otago Familial Bipolar Genetic Study

Objective: This paper outlines the methodologies used, and preliminary descriptive data collected, on a cohort of familial bipolar disorder (BPD) probands and first-degree relatives taking part in a descriptive and genetic study into familial BPD in New Zealand. Method: Fifity-five bipolar probands and 67 first-degree relatives were interviewed using the modified Diagnostic Interview for Genetic Studies (DIGS) and Family Interview for Genetic Studies (FIGS). Data was also collated from other sources. Blood samples were taken for DNA genomic analysis. Results: New Zealand families in which BPD segregates proved willing participants in this familial based genetic research. The methodologies used were acceptable. High rates of comorbidity were found in probands (27.3% met DSM-IV criteria for panic disorder/sub-threshold panic disorder; 12.7% for phobic disorder; 1.8% for obsessive-compulsive disorder; 9.1% for alcohol-related disorders and 7.3% for an eating disorder) and relatives (major depression 34.3%; panic disorder/sub-threshold panic disorder 12.0%; phobias 11.9% and alcohol-related disorders 11.9%). The polarity of index BPD illness was related to age of onset and frequency of comorbidity. Suicidal behaviour was common. Conclusions: Psychiatric genetic research in New Zealand families is highly feasible. Emerging trends in the familial transmission of BPD include high rates of comorbidity, illness patterns based on polarity of index episode and frequent suicidal behaviour. Such trends will be delineated further as numbers accrue, perhaps enabling identification of more homogenous phenotypic subgroups than currently produced by diagnostic schemes.

Tardive dyskinesia in bipolar affective disorder : a catchment area study

The prevalence of tardive dyskinesia in a consecutive series of 69 patients with bipolar affective disorder admitted to a catchment area service was found to be 19%. Prevalence increased with age and was related to the age of onset of bipolar disorder and number of previous episodes. Patients with tardive dyskinesia were significantly slower on a simple test of cognitive function (Trails B).

How effective is lithium in the prevention of relapse in bipolar disorder? A prospective naturalistic follow-up study

Objective: The effectiveness of lithium in preventing recurrences of bipolar disorder was examined prospectively for 2 years in two representative samples of bipolar I patients being treated in a comprehensive program following recommended guidelines. Method: One hundred and twenty patients were recruited from consecutive admissions to two catchment area psychiatric services (one in the United Kingdom, the other in New Zealand). They were seen at 3–monthly intervals by a member of the research team. Treatment was adjusted according to clinical needs. Results: Overall, two-thirds of the patients had a recurrence. Of the 57 on lithium as sole treatment, 39 (68%) had a further episode; 17 after stopping lithium. The 42 on other mood stabilisers and/or an antipsychotic, with or without lithium, did no better. By contrast, only eight (38%) of the 21 who were taking no prophylactic medication had a recurrence. Conclusions: Lithium is much less effective in clinical practice than would be expected from clinical trial results. A major reason for this is poor compliance. Alternative treatment strategies are needed to improve the outcome for bipolar disorder patients