Which antidepressant?

Although depression may affect as many as half of people with Parkinson's disease (PD) there is little evidence to support the selection of an appropriate antidepressant.

In a trial funded by the National Institute of Neurologic Disorders and Stroke, US psychiatrists randomised 52 patients with PD and depression to treatment with nor‐triptyline or controlled‐release paroxetine, or to placebo for eight weeks (Neurology 2008;doi:10.1212/ 01.wnl.0000336340.89821.b3).

Nortriptyline, but not paroxetine, was superior to placebo for the change in Hamilton Depression Rating Scale (HAM‐D) score (from 19–21 to 11, 12 and 16 respectively) and overall response rate (53, 11 and 24 per cent respectively). Nortrip‐tyline was superior to placebo but not to paroxetine for sleep improvement, social functioning and anxiety. For nortriptyline, numbers needed to treat for a response were 3.5 vs placebo and 2.4 vs paroxetine. Drop‐out rates were high (29–39 per cent) but there was no significant difference between the groups.

Does galantamine improve cognitive function?

Limited evidence suggests that nicotinic stimulation in patients with PD has mixed benefits but that cholinesterase inhibitors may reduce dementia symptoms, prompting a US trial to determine the impact of galantamine on cognitive function in 69 patients with PD but not dementia (J Neurol Neurosurg Psychiatry 2009;80: 18–23).

After escalating the dose of galantamine from 8mg daily to 24mg daily over 16 weeks, there were no differences from placebo in any measures of cognitive function, behaviour or motor function. Galantamine was poorly tolerated, with 39 per cent of patients stopping treatment prematurely compared with 16 per cent assigned to placebo. The most frequent adverse events were gastrointestinal intolerance, worsening PD symptoms, tremor and deterioration in mood or cognition.

Natalizumab for paediatric MS

Neurologists in Germany have reported success using natalizumab to treat refractory relapsing‐remitting multiple sclerosis in three children (Arch Neurol 2008;65:1655‐8).

After failure of interferon beta or glatiramer acetate and multiple relapses, treatment with natalizumab was initiated to three children aged 12, 16 and 17 years. The initial dosage was 3mg per kg every four weeks in the youngest child and 5mg per kg in the others. In the 17‐year‐old patient, natalizumab was associated with an increase in infections and the dose was reduced to 3mg per kg without further incident.

After treatment for 15 to 24 months, there was no evidence of disease progression and MRI revealed no new lesions. Treatment was well tolerated. The authors say their series brings to four the number of reported cases of successful natalizumab therapy in children with multiple sclerosis.

Atypicals affect sexual function differently

Aripiprazole is associated with greater improvement in sexual function than olanzapine, risperidone or quetiapine in patients with schizophrenia living in the community (BMC Psychiatry 2008;8:95 doi:10.1186/1471‐244X‐8‐95).

This non‐blinded 26‐week naturalistic trial in 555 patients found sustained improvement with aripiprazole beginning after eight weeks of treatment. Among the other atypicals, quetiapine was superior to olanzapine and risperidone. Aripiprazole was associated with a greater reduction in serum prolactin levels than olanzapine or quetiapine whereas prolactin levels increased with risperidone. However, there was no correlation between sexual function and prolactin levels.

The incidence of weight gain (12 per cent) and medication change due to poor symptom control (23–32 per cent) were similar for aripiprazole and other atypicals.

Ethnicity influences metabolic risk A post hoc analysis of trial data suggests that aripiprazole is associated with a lower risk of metabolic syndrome than olanzapine – but this difference is more marked among white people than those of African American or Hispanic origin (J Clin Psychiatry 2008; pii ej08m04267).

Metabolic syndrome is a risk factor for cardiovascular disease and diabetes. In this trial in 314 patients with acute schizophrenia designed to assess safety and tolerability, aripiprazole was associated with a significantly reduced risk of metabolic syndrome compared with olanzapine in all patients (odds ratio 0.33) and in white patients alone (OR 0.20). However, the difference was much smaller (OR 0.53), and not statistically significant, in black or Hispanic patients. The incidence of metabolic syndrome in white patients was 17 per cent with ari‐piprazole and 32.5 per cent with olanzapine; in patients of black or Hispanic origin, the corresponding figures were 25 and 33 per cent.

Postnatal depression: concerns about antidepressants

Little is known about how women with postnatal depression view treatment with antidepressants. UK investigators now report a qualitative analysis of treatment perceptions based on interviews with 27 participants in a trial comparing antidepressants and counselling (Family Practice 2008;25:450‐5).

Most women had hoped to receive counselling, with only four saying they initially wanted drug therapy. Those who wanted an anti‐depressant felt they needed a ‘lift’, felt no need for counselling and had no worries about medication; three had previously taken an anti‐depressant.

Those who wanted counselling felt a need to talk and could not confide in friends or family; some did not want to visit their GP, fearing they would be prescribed medication without being listened to. They believed that counselling was more effective and they held unfavourable views about antidepressants, concerned about dependence, social stigma and being judged a poor mother.

Some women requested a low dose or close supervision and remained uncomfortable about taking an antidepressant despite experiencing benefits from treatment. Seven of the 16 prescribed an anti‐depressant continued treatment; those who stopped did so because they felt better, in some cases without consulting the GP.

The authors say that women with postnatal depression share the misgivings of others with depression about their treatment. Their views about antidepressants should therefore be assessed and addressed individually. These views can change, the authors say, and GPs can have a key role in this process.

Adherence after remission of recurrent depression

Most patients in remission after at least two episodes of depression may be non‐adherent with their medication, a study from The Netherlands shows (J Clin Psychiatry 2008; pii:ej08m04119).

In 91 participants in a trial of cognitive behavioural therapy for relapse prevention, 69 per cent said they had missed at least 20 per cent of the doses of their antidepressant at some time over a two‐year period. The only factors significantly associated with non‐adherence were higher levels of education and higher personal pathology (less adaptive capability) but these explained only 15 per cent of the variance.

There are no consistent predictors of non‐adherence in this group of patients, the authors conclude, so doctors should be continuously aware of the risk and discuss it with their patients during all phases of treatment.

Metabolic effects of valproate

Patients with bipolar disorder who gain weight during valproate therapy have metabolic changes that are different from those in matched controls, say investigators from New Zealand (Austr NZ J Psychiatry 2009;43:53‐60).

They compared 60 overweight patients with bipolar disorder (mean body mass index, BMI, 34kg per m²) who had gained an average of 15kg during up to five years' treatment with sodium valproate with controls with no psychiatric illness matched for age, sex, BMI and ethnicity.

Valproate was associated with a higher frequency of metabolic syndrome (50 vs 32 per cent; p=0.06) and dyslipidaemia (lower HDL‐cholesterol and raised triglyceride levels). However, there were no differences in waist circumference, levels of insulin or insulin resistance. Levels of adiponectin, a cytokine that protects against metabolic disease, were higher in patients taking valproate. The use of atypical antipsychotics did not influence the prevalence of metabolic syndrome.

Add‐on lamotrigine for bipolar depression

Patients who experience a major depressive episode during treatment with lithium may benefit from adjunctive lamotrigine, say Dutch investigators (J Clin Psychiatry 2008;pii:ej08m04152).

Their eight‐week placebo‐controlled trial in 124 patients found that lamotrigine (titrated to 200mg daily) significantly reduced MontgomeryÅsberg Depression Rating Scale (MADRS) score (by 15 vs 11 points with placebo). Response rates (reduction in MADRS score ≥50 per cent or a much improved change of depression score on Clinical Global Impressions – Bipolar (CGI‐BP) scale) were higher with lamotrigine (52 vs 32 per cent), though the difference according to just the CGI‐BP scale was not statistically significant (64 vs 49 per cent).

Two serious adverse events were possibly related to lamotrigine: one case of mania and one of deterioration of depression, both of which required admission. A hypomanic episode occurred in four patients taking lamotrigine and two taking placebo. Copyright © 2009 Wiley Interface Ltd