Sumatriptan challenge in bipolar patients with and without migraine: a neuroendocrine study of 5-HT1D receptor function.

An association between bipolar disorder and migraine has been lately recognized and an abnormality of central serotonergic function is suggested as the underlying neurophysiological disturbance. To examine the role of serotonin in bipolar disorder and migraine, we used the neuroendocrine challenge paradigm, and we chose sumatriptan, a 5HT1D agonist, as the pharmacological probe. We studied nine bipolar patients with migraine, nine bipolar patients without it, seven migraine patients, and nine matched normal controls. A post-hoc analysis showed subsensitivity of serotonergic function, reflected in a blunted growth hormone response to sumatriptan challenge in bipolar patients who also suffered from migraine.

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.

Moclobemide vs. imipramine in bipolar depression: a multicentre double-blind clinical trial.

OBJECTIVE: To determine the relative efficacy, tolerability and risk of precipitating mania of moclobemide and imipramine in the treatment of bipolar depression. METHOD: A randomized, double-blind, parallel group, multicentre study of moclobemide (MCB) (450-750 mg daily) and imipramine (IMI) (150-250 mg daily) in 21 centres in nine countries; 156 patients (65 males, 91 females) aged 18-65 with bipolar depression (17-item Hamilton Depression Rating Scale (HAMD) score chi16) participated. Clinical status was assessed using standardized rating scales before treatment and at 1,2,3,4,6 and 8 weeks. The data were analysed on an intention to treat basis with the last observation carried forward. RESULTS: In the MCB group, the mean HAMD fell from 23.0 to 13.1, in the IMI group it fell from 22.5 to 9.5; the mean score on the Montgomery-Asberg Depression Rating Scale (MADRS) fell from 29.5 to 16.3 on MCB and from 29.2 to 11.6 on IMI. There were no statistically significant differences between the two groups on any efficacy measures. Anticholinergic side-effects were three times more common with IMI than MCB and weight gain was also greater on IMI. Two patients (3.7%) on MCB and six patients (11%) on IMI were withdrawn because of manic symptoms, with manic symptoms occurring earlier on IMI, although these differences did not reach statistical significance. CONCLUSION: No differences in efficacy were detected between MCB and IMI in the treatment of bipolar depression. The data suggests that MCB is less likely than IMI to precipitate mania.

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.

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.

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: Fifty-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.

Skin problems and parasites in children: 3--Head lice.

Head lice are common in children, occur occasionally in women and are rare in men. All social classes are affected. Treatment should be reserved for genuine cases of infestation, i.e. where live lice are seen. More research is needed into methods of treating head lice. The school nurse has an important role in educating children, parents and school staff.

Clozapine in the management of bipolar and schizoaffective manic episodes resistant to standard treatment.

OBJECTIVE: To test the efficacy of clozapine in treatment-resistant manic episodes. CLINICAL PICTURE: Three cases, two with bipolar disorder (manic) and one of schizoaffective disorder (manic), were treated with clozapine. TREATMENT: Clozapine was used after the failure of standard antipsychotics and mood stabilizers. OUTCOME: All three cases were successfully treated. CONCLUSION: A controlled trial of clozapine in treatment-resistant bipolar and schizoaffective manic episodes is indicated.

Condoms: still the most popular contraceptive.

Condoms can be used as a barrier contraceptive and/or to protect against many sexually-transmitted diseases. They are easy to buy and use and free from medical risk. Carefully used, and used in conjunction with a spermicide, condoms have similar reliability to IUDs, progesterone-only pills and the diaphragm. The condom must be put on before the penis touches the vaginal area. The penis should not touch the vaginal area after the condom has been taken off. Oil-based products, eg baby oil, massage oil, lipstick, petroleum jelly, suntan oil, can damage the condom. If a lubricant is required, use one that is water-based.

PIP: Easy to buy and use, and free from medical risk, the condom is the most commonly used contraceptive in the UK. Condoms are highly reliable when used properly and help protect against most sexually transmitted infections. Condom use may also help to protect against cervical cancer. However, on the down side, condoms can interrupt love-making, need to be used carefully, and some people report that they reduce sexual sensation. Because condoms are so widely used, nurses, midwives, and other health professionals may mistakenly assume that everyone knows how to use them correctly and that there is no need to offer detailed advice on the method. Nurses and pharmacists can help teach men and women about condom use. When advising on male condoms, health professionals should remind clients of the relevant safety points, advise them to choose high quality condoms, make sure that the condoms are not beyond their expiration date, and to use each condom only once. Condoms and pharmacies, choosing a contraceptive method, common condom-use errors, choosing the appropriate condom, and the female condom are discussed.

Coughs and colds: advising on what to take.

Take special care when recommending a product to people with a pre-existing medical condition (e.g., high blood pressure, stomach problems, asthma). It is safer to advise them to consult their pharmacist or doctor if there is a possibility of adverse drug interaction. Be aware of the possibility of overdosage (e.g., some patients take a large number of remedies simultaneously and may unwittingly be taking too much paracetamol, aspirin or ibuprofen). Green or yellow sputum suggests the patient has a bacterial infection in addition to a cold, and consulting a doctor is advisable. Enquire whether a cough is productive ("loose" or "chesty") or non-productive "dry, "tricky" or "irritating") so that you can advise on appropriate product. Productive coughs are helped by expectorants. Dry coughs are helped by suppressants. Cough preparations often contain antihistamine which may cause drowsiness, so be aware of this when advising a patient. For young children a paediatric formulation is advisable. Many of the main brands of cough and cold medicines have infant or junior varieties. Vapour products, often using substances like menthol placed on a tissue near the child but out of reach, can be very effective for blocked noses. Sugar-free preparations should be used for children (and adults) where possible, to avoid the risk of tooth decay. If patients suffer from repeated colds and coughs, and complain of feeling "run down", questioning may reveal that they have a poor diet. In that case, recommending a vitamin supplement or tonic and advice on a healthier diet may be appropriate. A persistent cough should receive medical attention.

The effects of D- and L-fenfluramine (and their interactions with D-amphetamine) on psychomotor function and mood.

This study reports the results on psychomotor functioning of D- and L-fenfluramine alone, and in combination with D-amphetamine, in a placebo-controlled trial on 12 normal male volunteers, in order to investigate their CNS activity in humans. The major findings were that D-amphetamine increased alertness, L-fenfluramine increased unhappiness whilst D-fenfluramine decreased hunger and increased the critical flicker fusion threshold. D-Amphetamine in combination with D-fenfluramine increased the critical flicker fusion threshold and in combination with L-fenfluramine the alerting action was diminished. The differing actions of the fenfluramine isomers and their interactions with D-amphetamine suggest that D-fenfluramine is predominantly serotonergic in its activity, whereas L-fenfluramine may be causing dopamine blockade, reducing certain actions of amphetamine possibly mediated by dopamine receptors. The significance of these results in relationship to the psychopharmacology of serotonin, dopamine, and noradrenaline is discussed.

Long term treatment of bipolar disorder.

Bipolar 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.

Risperidone appears safe in patients with antipsychotic-induced blood dyscrasias.

Two cases are reported who developed blood dyscrasias, involving neutropenia and thrombocytopenia respectively, after treatment with phenothiazine and butyrophenone antipsychotics. A subsequent good therapeutic response was obtained with risperidone. It is suggested that risperidone may be considered as an alternative when blood dyscrasias occur with classic antipsychotics.

Is there a seasonal pattern of relapse in bipolar affective disorders? A dual northern and southern hemisphere cohort study.

BACKGROUND: Admission statistics for mania frequently show an increase in the summer. The present two-centre study was designed to test the hypothesis, in a representative sample of bipolar patients, that manic and depressive relapses show a seasonal pattern. METHOD: Two cohorts of bipolar I patients, one in London, England (n = 86), the other in Dunedin, New Zealand (n = 58), were tracked retrospectively during 1985-88 and prospectively during 1989-91, with the onset of all relapses being carefully dated. RESULTS: In the London cohort there were 221 episodes of mania and 76 of depression; in the Dunedin cohort there were 201 of mania and 61 of depression. No consistent seasonal pattern of mania was detected in either centre. There was an autumn preponderance of depressive episodes in both centres. CONCLUSIONS: Relapse of bipolar depression, but not of mania, appears to be determined in part by seasonal factors.

Does puerperal illness distinguish a subgroup of bipolar patients?

Puerperal psychosis was found to be the 1st illness for 13 (36%) of a series of 36 mothers with bipolar affective disorder. The risk of recurrence with childbirth in those with established bipolar disorder was found to be 25-40%. Those women who survived childbirth without illness but then became ill at a later time reported a worse illness course. Recent fatherhood was not a precipitant of 1st affective illness for any of the 28 bipolar men.