The N‐methyl‐D‐aspartic acid (NMDA) agonist D‐cycloserine appears to augment the effectiveness of behavioural therapy: this has been demonstrated in animal models and in patients with a fear of heights and social anxiety disorder. It appears to be an effect on learning rather than mood. By contrast, there have been inconsistent results in patients with obsessive‐compulsive disorder (OCD), as US investigators have again reported (Am J Psychiatry 2008;165:335‐41).

Their placebo‐controlled study evaluated the efficacy of adding D‐cycloserine to 10 twice‐weekly behaviour therapy sessions; a 100mg dose was administered one hour before therapy. Of the 23 patients randomised, 16 were also taking other psychotropic medication.

D‐cycloserine was associated with a large treatment effect on the Yale‐Brown Obsessive Compulsive Scale mid‐way through the trial but not one month after completion. Active treatment was also associated with significantly fewer depression symptoms immediately after treatment –again, with a large effect size not persisting one month later. No adverse effects were reported.

The authors speculate that the enhanced early response might help to reduce the proportion of patients who discontinue therapy early.

Among adolescents with depression, the response to initial treatment with an SSRI is about 60 per cent. There is a lack of evidence to show which strategy is then most effective but a large US trial has now compared the efficacy and safety of switching to another antidepressant (an SSRI or venlafaxine) with or without cognitive behaviour therapy (CBT) (JAMA 2008;299:901–13).

Initial treatment failure was defined as clinically significant depression despite at least eight weeks' treatment with an SSRI, the last four weeks at a dose equivalent to fluoxetine 40mg daily. A total of 334 patients were then randomised to one of the four treatment arms, with dose titration over the first four to six weeks. CBT involved up to 12 sessions, in addition to family therapy for all participants.

The mean duration of previous treatment with an SSRI was 17 weeks and participants had undergone a median of eight psychotherapy sessions in the preceding 12 weeks.

After 12 weeks, an adequate clinical response occurred in 55 per cent of patients assigned to CBT plus either antidepressant and 41 per cent with an antidepressant alone. There was no difference in efficacy between the antidepressants, alone or in combination, but venlafaxine was associated with more skin problems (8 per cent versus 2 per cent with an SSRI) and a greater increase in diastolic blood pressure and pulse.

There is a small advantage from switching to a non‐SSRI if initial treatment with an SSRI fails in adults with depression, according to a meta‐analysis of four randomised trials (Biol Psychiatry 2008;63:699–704).

The analysis, involving a total of 1496 patients with depression resistant to various SSRIs, found that those switched to venlafaxine, bupropion or mirtazapine were 28 per cent more likely to achieve remission; however, the absolute difference was small (4.5 per cent) and there was no difference in response rates. Treatment discontinuation was less likely after switching to another SSRI (12 versus 18 per cent) but the difference was not statistically significant.

Repeating the analysis on trials switching to venlafaxine only, there was a similar advantage in remission rate (31 per cent) but no difference in treatment discontinuation from an SSRI.

The authors estimate a number needed to treat of 22 to achieve one additional remission by switching to a non‐SSRI rather than a second SSRI.

Current evidence suggests no clear difference in efficacy for CBT over antidepressants in the treatment of panic disorder and it is unclear whether combining the two improves efficacy. Researchers from The Netherlands now report a three‐way comparison of CBT, an SSRI and their combination in 150 patients with panic disorder with or without agoraphobia (Acta Psychiatr Scand 2008;117:260–70).

Almost 30 per cent of participants withdrew from the trial before completion –most frequently due to adverse effects (24 per cent) or poor compliance (22 per cent); they were also significantly more likely to have previously used an SSRI.

After nine months, intent‐totreat analysis showed that CBT plus SSRI was superior to CBT alone but not to SSRI monotherapy; there was no difference between CBT or an SSRI as monotherapy.

It is known that maternal marijuana smoking is associated with impaired intellectual development in three year olds, as defined by measures of verbal reasoning and short‐term memory. US investigators have now repeated their assessments in children reaching the age of six years (J Am Acad Child Adolesc Psychiatry 2008;47:254–63).

The cohort included 648 children born to mothers from a low income population who reported smoking at least two joints per month or three or more alcoholic drinks per week during the first trimester. Marijuana use during pregnancy was associated with greater use of cocaine, tobacco and alcohol compared with women who abstained from marijuana.

Light to moderate maternal use of marijuana (an average of less than one joint daily) was not associated with impaired cognitive development. Assessments at three years old had suggested intellectual development was unaffected by marijuana exposure; that was not the case for six year olds whose mothers were heavy users (an average of one or more joints daily). Heavy use during the first trimester was associated with lower verbal reasoning scores; during the second trimester it was associated with short‐term memory deficits; and during the third it was associated with poorer quantitative reasoning.

Activation of protein kinase C (PKC) appears to play an important role in manic episodes in people with bipolar disorder. The oestrogen receptor antagonist tamoxifen is also a centrally active inhibitor of PKC, prompting investigators in Turkey to carry out a pilot study of its effects in mania (Arch Gen Psychiatry 2008;65:255–63).

They randomised 66 patients with bipolar 1 disorder who were experiencing a current manic or mixed episode to placebo or tamoxifen 20mg twice daily; adjunctive lorazepam 5mg daily was permitted. After three weeks, tamoxifen reduced mean scores on the Young Mania Rating Scale (YMRS, ‐5.84 points per week) and Clinical Global Impressions‐mania (‐0.73 points per week) compared with weekly increases in both among placebo recipients (1.50 and 0.10 respectively); these differences were statistically significant. The response to tamoxifen was consistent across individual YMRS items and these changes were supported by trends to improvement in secondary endpoints assessing psychotic symptoms and depression, and less use of lorazepam. Tamoxifen was also associated with higher rates of response (48 versus 5 per cent with placebo) and remission (28 versus 0 per cent). Adverse events were reported by 20 per cent of patients taking tamoxifen and by 10 per cent with placebo.

A trial to determine the effects of ginkgo biloba extract on cognitive decline in older people has proved inconclusive (Neurology 2008; 70:published online ahead of print).

The 42‐month study randomised 118 healthy people aged over 84 years to placebo or a standardised extract of ginkgo biloba. The herb was associated with a reduced rate of cognitive decline and memory loss compared with placebo, though this did not achieve statistical significance on intent‐to‐treat analysis.

After adjustment for medication adherence (65 per cent with ginkgo biloba, 72 per cent with placebo), treatment was associated with a protective effect against cognitive decline but this disappeared after controlling for other covariates. Stroke and transient ischaemic attack were more frequent among participants taking ginkgo biloba (12 versus 0 per cent) but mortality was similar.

Scottish psychiatrists have reported a review of 11 250 case records for all clinical contacts in Lanarkshire between 2002 and 2005 (J Clin Psychiatry 2008;69: 240–5).

They found that 2 013 people (18 per cent) had been prescribed an atypical antipsychotic, though records were adequate for analysis for only 1464.

Clozapine was almost exclusively prescribed for schizophrenia but patterns of use for other atypicals differed. Schizophrenia accounted for 39–63 per cent of indications, depression/anxiety for 21–34 per cent and bipolar disorder for 5–21 per cent.

In patients with schizophrenia, 81 per cent of those prescribed olanzapine were also given an antidepressant; the corresponding figure for risperidone was 18 per cent. The frequency of prescribing a second antipsychotic ranged from 40 per cent with olanzapine to 3 per cent with clozapine.

Discontinuation rates were highest with olanzapine (60 per cent) and lowest with clozapine (7 per cent). Adverse effects and lack of efficacy were equally common reasons for discontinuation. Mean time to discontinuation was shorter for quetiapine (191 days) and risperidone (152 days) than for amisulpride (232 days), olanzapine (256 days) or clozapine (427 days).

Two trials have reported strategies for tackling weight gain associated with atypical antipsychotics.

Investigators in Finland evaluated the efficacy of orlistat 120mg three times daily in 63 patients taking clozapine or olanzapine with a mean body mass index of approximately 33kg per m² (J Clin Psychiatry 2008; published online ahead of print).

After 16 weeks, there was no overall difference between orlistat and placebo in mean weight loss. Men, but not women, lost significantly more weight with orlistat than placebo. There was no difference in response between patients taking clozapine or olanzapine.

The second study, from China, evaluated the efficacy of metformin in preventing weight gain associated with olanzapine (Am J Psychiatry 2008;165:352–8). Thirty‐seven inpatients reporting no use of antipsychotics in the preceding three months were treated with olanzapine 15mg daily and randomised to placebo or metformin 750mg daily.

After 12 weeks, metformin was associated with significantly less mean weight gain (1.90kg versus 6.87kg), supported by lower mean body mass index, waist circumference and waist‐to‐hip ratio. There was no difference in mean fasting blood glucose but fasting insulin levels and insulin resistance were lower in patients taking metformin. There was no difference in reported adverse effects.

Mycophenolate mofetil is an effective treatment for ocular myasthenia, according to a report of a case series from the USA (J Neurol 2008;published online doi:10.1007/ s00415–008‐0718‐9).

Thirty‐one consecutive patients attending a specialist practice were treated with prednisone 40‐60mg daily and mycophenolate mofetil titrated to a target dose of 1.0g daily. The steroid was tapered off when symptom control was achieved. Breakthrough symptoms were treated with pyridostigmine 3060mg four‐hourly.

Mean follow‐up was 4.2 years; four patients discontinued mycophenolate mofetil in the first four months due to cost in one patient and diarrhoea and vomiting in the others. Disease progression was arrested in those who continued mycophenolate mofetil. Symptom breakthrough occurred in seven patients; adverse effects included nausea (nine patients), diarrhoea (five) and vomiting (one).

A small trial has shown that levetiracetam substantially reduces the severity of tardive dyskinesia secondary to antipsychotic therapy (J Clin Psychiatry 2008; published online ahead of print).

Fifty patients (mean AIMS score 8.0–9.4) were randomised to placebo or levetiracetam titrated from 500mg daily to 3000mg daily depending on tolerability; the mean dose after 12 weeks was 1900mg daily. Completion rates were 64 per cent with levetiracetam and 80 per cent with placebo but the difference was not statistically significant.

Levetiracetam significantly reduced the AIMS score compared with placebo (by 44 versus 19 per cent), the difference becoming statistically significant after six weeks. Of 15 patients randomised to levetiracetam who entered an open‐label continuation phase, 11 completed a further 12 weeks' treatment at a mean final dose of 2156mg daily. The AIMS score decreased further to a total reduction of 58 per cent compared with baseline.

People with spinocerebellar ataxia have difficulty reading due to abnormal eye movements and hypermetria. A report of successful treatment in two brothers suggests that the N‐methyl‐D‐aspartic acid (NMDA) receptor antagonist memantine may be an effective treatment (Neurology 2008;70: 810–2).

Despite perfect vision, neither brother could read due to the severity of saccadic eye movements. Memantine was titrated up to a dose of 20mg daily over one month, achieving sustained improvement without significant adverse effects in both cases. The frequency of saccadic movements decreased from 154–168 per minute to 69–89 per minute though the amplitude of movements was reduced in only one brother.

The authors speculate that memantine may block NMDA receptors on mossy fibre synapses on cerebellar nuclei, reducing the inputs that trigger saccadic movements.

Audit of specialist and shared care drug misuse services in Hertfordshire in 2003 and 2005 has revealed improvements in services after the introduction of the new contract for GPs. However, service capacity has not increased as expected (Psychiatric Bull 2008; 32:88–90).

The number of surgeries involved in shared care decreased from 18 to 14; whereas as client numbers in specialist services increased by more than half there was little change in shared care. However, there were no instances of prescribing outside guidelines in shared care in 2005 (versus two in 2003). More clients in shared care (33 versus 20 per cent) were prescribed buprenorphine in 2005 and the doses prescribed for methadone substitution corresponded more closely with those used in specialist services. More clients in shared care were in paid employment and living in accommodation, consistent with regional criteria.

The National Society for Epilepsy (NSE) has launched a new A2 colour ‘pill poster’ featuring all the currently available branded antiepileptic drugs (AEDs).

NSE, the UK's leading epilepsy charity, supported by a grant from pharmaceutical company Eisai, have designed the poster for professionals who work with individuals with epilepsy.

Rona Gibb, epilepsy information manager at NSE said ‘We get calls from individuals taking antiepileptic drugs to treat their epilepsy, and they often have questions about the drugs themselves. Having this poster available in surgeries, clinics and pharmacies, where they will be most useful, means that information is on‐hand if individuals want to discuss their treatment. It will also provide an opportunity for healthcare professionals to engage in meaningful discussions about epilepsy treatment with the individuals that they see.’ Further information from: Epilepsy Information Services on 01494 601 392 or email: EISadministrator.org.uk Copyright © 2008 Wiley Interface Ltd