Combined drug therapy for at least 36 weeks reduces relapse after psychotic depression

Patients with psychotic depression who achieve remission benefit from continuing the antipsychotic drug olanzapine, alongside the antidepressant sertraline for at least a further four months, a North American trial has found | JAMA | via National Institute for Health Research

A randomised controlled trial has found that patients who reduced and stopped olanzapine when their condition stabilised were more than twice as likely to relapse when compared with those who continued combined drug therapy. The majority of relapses occurred within two months of withdrawing olanzapine.

The trial, with 126 participants found that by 36 weeks from stabilisation, 13 people (20.3%) who were taking sertraline plus olanzapine and 34 people (54%) who were taking sertraline plus placebo experienced a relapse.

These results suggest that continuation of combined drug therapy for these patients may help reduce the risks of potentially life-threatening relapse. The benefit needs to be balanced against the adverse effects of olanzapine, which include weight gain.

Full story at National Institute for Health Research

Full reference: Flint AJ, Meyers B, Rothschild AJ et al. | Effect of continuing olanzapine vs placebo on relapse among patients with psychotic depression in remission: the STOP-PD II randomized clinical trial| JAMA | 2019;322(7) | 622-31.

NICE updates antidepressant guidelines to reflect severity and length of withdrawal symptoms

BMJ | 2019| NICE updates antidepressant guidelines to reflect severity and length of withdrawal symptoms| 367| BMJ | doi: https://doi.org/10.1136/bmj.l6103 (Published 18 October 2019)

The National Institute for Health and Care Excellence (NICE) has amended its guidelines on depression to recognise the severity and length of antidepressant withdrawal symptoms.

The guidance on treating depression in adults now states that withdrawal symptoms may be severe and protracted in some patients.

NICE’s previous guideline, which was originally published in 2009 and updated last year, said that withdrawal symptoms are “usually mild and self limiting over about one week.”

But in an amendment, NICE acknowledges that “there is substantial variation in people’s experience, with symptoms lasting much longer (sometimes months or more) and being more severe for some patients.”

Clinicians should “advise people taking antidepressant medication that, before stopping it, they should discuss this with their practitioner,” the updated guideline says.

Read the full article from The BMJ 

Antidepressants and Depression

Position statement on antidepressants and depression | Royal College of Psychiatrists

This position statement sets outs the Royal College of Psychiatrists’ view on promoting optimal use and management of antidepressants. It discusses the challenges with prescribing antidepressants, including considering the evidence around efficacy, benefits and harms, ensuring they are used when clinically indicated and managing withdrawal. The statement includes range of recommendations aimed at the UK health departments, national bodies and commissioners.

Full document available here

NIHR Signal: Combining mirtazapine with other antidepressants is not effective for treatment-resistant depression

NIHR | February 2019|Combining mirtazapine with other antidepressants is not effective for treatment-resistant depression

An NIHR Signal is highlighting the findings of a trial that found adding mirtazapine to first-line antidepressants for adults with treatment-resistant depression does not improve symptoms when compared with placebo (dummy pills). People taking mirtazapine are more likely to experience side effects, and stop taking their treatment.

This NIHR-funded trial took place in 106 general practices in England, recruiting 480 adults with mild to severe depression. All participants had been taking selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI) antidepressants for at least six weeks but were still depressed.

Read the NIHR Signal here 

Read our blog post on this Study finds combining mirtazapine with other antidepressants is not effective for treatment-resistant depression in a sample of depressed patients

Study finds combining mirtazapine with other antidepressants is not effective for treatment-resistant depression in a sample of depressed patients

NIHR | January 2019 | Combining mirtazapine with other antidepressants is not effective for treatment-resistant depression

The findings of a  randomised controlled trial (RCT) which recruited 480 adults with moderate-severe depression at baseline all had been taking a SSRI or SNRI for at least six weeks but were still experiencing depressive symptoms, has now been publsihed as an NIHR Signal. Participants were screened with Beck’s Depression Inventory (BDII);a scale 0 to 63, with high scores (over 29) indicating severe depression and scores below 26 indicating mild depression.

Following randomisation half of the sample (241) took their prescribed SSRI or SNRI, in addition they also received one 15mg capsule of mirtazapine daily for a fortnight, followed by two 15mg capsules for up to 50 weeks. The other 50 per cent (239)  were given identical placebos.

• After 12 weeks both groups had improved substantially, but there was little difference in severity of depression symptoms between the groups, suggesting that treatment with the SSRI or SNRI continues to have an effect for more than six weeks.
• Adverse events were more common in the mirtazapine group with half  of the sample reporting side effects, compared with almost a thrid (30%) in the placebo group.
• People in the mirtazapine group were more likely to stop taking their trial drug. Of the 121 people taking mirtazapine who reported side effects, 46 stopped taking it. In the placebo group, 71 people reported adverse events, and 9 of them stopped.

The NIHR Signal reports that the  trial did not show any benefit in taking mirtazapine in combination with SSRI or SNRI antidepressants for people who had shown resistance to initial treatment.

The NICE guideline is currently being updated with an an anticipated publication date of December 2019 (Source: NIHR Signal).

Read the Signal Combining mirtazapine with other antidepressants is not effective for treatment-resistant depression

Full reference:

Kessler, D. | 2018|  Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR)|  bmj, 363, k4218.

Objective To investigate the effectiveness of combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants for treatment resistant depression in primary care.
Design Two parallel group multicentre phase III randomised placebo controlled trial.

Setting 106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015.

Participants 480 adults aged 18 or more years who scored 14 or more on the Beck depression inventory, second revision, fulfilled ICD-10 (international classification of diseases, 10th revision) criteria for depression, and had used an SSRI or SNRI for at least six weeks but were still depressed. 241 were randomised to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment. Participants were stratified by centre and minimised by baseline Beck depression inventory score, sex, and current psychological therapy. They were followed up at 12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12 week follow-up.

Main outcome measures Depressive symptoms at 12 weeks after randomisation, measured using the Beck depression inventory II score as a continuous variable. Secondary outcomes included measures of anxiety, quality of life, and adverse effects at 12, 24, and 52 weeks.

Results Beck depression inventory II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline scores and minimisation or stratification variables, although the confidence interval included the null (mean (SD) scores at 12 weeks. Adverse effects were more common in the mirtazapine group and were associated with the participants stopping the trial drug.

Conclusion This study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where evidence of effective treatment options is limited

Rotherham NHS staff  can request the article here

 

20 % of people who experience no improvement on antidepressants after a month need more time to respond

NIHR Signal | August 2018 | A fifth of people, who have no improvement on antidepressants at four weeks, respond if given more time

A new systematic review and meta-analysis is the first to ca that studied calculate the proportions of people with a delayed but positive response at different time points. Adult patients  with acute depression not yet responding to an antidepressant drug has a 1 in 5 chance of substantial symptom reduction between 5 and 8 weeks if they continue taking it. In those unresponsive after eight weeks, 1 in 10 will respond between 9 and 12 weeks. For the researchers, this has implications, for instance altering treatment plans too early can mean needlessly discarding first choice anti-depressants. These findings broadly support clinical guidance to wait for 3 to 8 weeks for antidepressants to work. This includes increasing support in the interim rather than switching to a less preferred antidepressant (NIHR).

Full details are from NIHR Signal