Category Archives: Mental Health

Study finds antidepressants to be more effective than placebos

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Major international study – comprising largest amount of unpublished data to date – has found that antidepressants are more effective than placebos for short-term treatment of acute depression in adults.

Meta-analysis of 522 trials compared 21 commonly used antidepressants and concluded all of them to be more effective than placebos for the short-term treatment of acute depression in adults, with effectiveness ranging from small to moderate for different drugs.

The trials analysed were all double-blind, randomised controlled trials (RCTs) with a total of 116,477 participants. The study includes the largest amount of previously unpublished data to date, all of which is now freely available online.

“Our study brings together the best available evidence to inform and guide doctors and patients in their treatment decisions. We found that the most commonly used antidepressants are more effective than placebos, with some more effective than others. Our findings are relevant for adults experiencing a first or second episode of depression – the typical population seen in general practice.” says lead author Dr Andrea Cipriani, University of Oxford and the NIHR Oxford Health Biomedical Research Centre.

Antidepressants can be an effective tool to treat major depression, but this does not necessarily mean that antidepressants should always be the first line of treatment.

“Medication should always be considered alongside other options, such as psychological therapies, where these are available. Patients should be aware of the potential benefits from antidepressants and always speak to the doctors about the most suitable treatment for them individually,” Ciprianiconcludes.

Large-scale worldwide illness

An estimated 350 million people have depression worldwide. The economic burden in the USA alone has been estimated at more than US$210 billion. Pharmacological and non-pharmacological treatments are available but owing to inadequate resources, antidepressants are more frequently used. However, there is considerable debate about their effectiveness.

As part of the study, the authors identified all double-blind RCTs that compared antidepressants with placebos, or with another antidepressant (head-to-head trials) for the acute treatment (over eight weeks) of major depression in adults aged 18 years or more. The authors then contacted pharma companies, original study authors, and regulatory agencies in order to supplement incomplete reports of the original papers, or provide data for unpublished studies.

Researchers use data mining to expedite effective prescriptions for depression patients…

The primary outcomes were efficacy (number of patients who responded to treatment, ie who had a reduction in depressive symptoms of 50% or more on a validated rating scale over eight weeks) and acceptability (proportion of patients who withdrew from the study for any reason by week eight).

Overall, 522 double-blind RCTs carried out between 1979 and 2016 that compared 21 commonly used antidepressants or placebos were included in the meta-analysis; the largest ever in psychiatry. A total of 87,052 participants had been randomly assigned to receive a drug, and 29,425 to receive placebos. The majority of patients had moderate-to-severe depression.

All 21 antidepressants were more effective than placebos and only one drug (clomipramine) was less acceptable than placebo.

Antidepressants effective to varying degrees

Some antidepressants were more effective than others, with agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine proving most effective, and fluoxetine, fluvoxamine, reboxetine, and trazodone being the least effective. The majority of the most effective antidepressants are now off patent and available in generic form.

Antidepressants also differed in terms of acceptability, with agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine proving most tolerable, and amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine being the least tolerable.

The authors note that the data included in the meta-analysis covers eight weeks of treatment, so may not necessarily apply to longer term drug treatment. The differences in efficacy and acceptability between different antidepressants were smaller when data from placebo-controlled trials were also considered.

Effects may not extend to bipolar condition

In order to ensure that the trials included in the meta-analysis were comparable, the authors excluded studies with patients who also had bipolar depression, symptoms of psychosis or treatment resistant depression, meaning that the findings may not apply to these patients.

“Antidepressants are effective drugs, but, unfortunately, we know that about one third of patients with depression will not respond. With effectiveness ranging from small to moderate for available antidepressants, it’s clear there is still a need to improve treatments further,” adds Dr Cipriani, .

Nothing is perfect

78% of the 522 trials were funded by pharma companies, and the authors retrieved unpublished information for 52% of the trials included in the meta-analysis. Overall, 9% of the trials were rated as high risk of bias, 78% as moderate, and 18% as low. The design of the network meta-analysis and inclusion of unpublished data is intended to reduce the impact of individual study bias as much as possible. Although this study included a significant amount of unpublished data, a certain amount could still not be retrieved.

“Antidepressants are routinely used worldwide yet there remains considerable debate about their effectiveness and tolerability. By bringing together published and unpublished data from over 500 double blind randomised controlled trials, this study represents the best currently available evidence base to guide the choice of pharmacological treatment for adults with acute depression. The large amount of data allowed more conclusive inferences and gave the opportunity also to explore potential biases,” says co-author Professor John Ioannidis, from the Departments of Medicine, Health Research and Policy, Biomedical Data Science, and Statistics, Stanford University, USA.

The international study was published in The Lancet.


Lundbeck and Otsuka start phase III for Rexulti in bipolar

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Otsuka and co-development partner Lundbeck have started two phase III trials of their atypical antipsychotic Rexulti in bipolar disorder, potentially adding a third indication for the drug.

The two companies have started enrolling patients into the two studies, which will evaluate Rexulti (brexpiprazole) as a treatment for manic episodes in bipolar patients that are accompanied by depressive symptoms and require hospitalisation.

First approved in 2015, Rexulti is currently available as an adjunctive therapy for adults with major depressive disorder as well as for schizophrenia and after a slow start, has seen its sales growth accelerate, with Lundbeck reporting turnover of the drug up 85% to $91m in the first half of the year.

It has a long way to go however before it can reach the heights of its predecessor – Abilify (aripiprazole) – which was a mainstay for both Lundbeck and Otsuka but has fallen off the patent cliff in recent years and seen steep sales decline as a result, although a long-acting depot formulation (Abilify Maintena) is still making gains.

To date Rexulti has only been launched in the US, Canada and Australia, although it was filed for approval in Europe in schizophrenia earlier this year.

The partners recently suffered a big setback in their plans for brexpiprazole after the drug posted mixed results in agitation in Alzheimer’s disease patients, a condition that affects millions of people worldwide. They were hoping brexpiprazole could become the first antipsychotic to be approved in that indication, but while one trial was positive, a second failed to hit the mark, leaving the future of the programme in doubt. They also were unable to convince the FDA that the drug improved cognitive function in patients with depression.

Approval for bipolar patients would not have the same large-scale opportunity but could still add momentum to the new drug as it would mean brexpiprazole would match the indications of Abilify. Lundbeck and Otsuka are also evaluating the drug in a phase II trial involving patients with post-traumatic stress disorder (PTSD).

The bipolar trials are comparing brexpiprazole to placebo on their ability to improve Young-Mania Rating Scale (YMRS) scores, a widely-used clinician rating scale.

Rexulti is one of a string of new drugs at Lundbeck – along with Abilify and antidepressant Brintellix (vortioxetine) – which it is banking on to help it weather the loss of patent protection for Abilify and former blockbuster antidepressant Lexapro/Celexa (escitalopram).


Otsuka recruits Medibio to pinpoint mental health biomarkers

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Otsuka has recruited mental health tech company Medibio to help assess the effectiveness of its schizophrenia and bipolar disorder treatment Abilify. 

Approved since 2002,  Abilify (aripiprazole) is both a dopamine partial agonist and serotonin antagonist – two mechanisms thought to play key roles in a range of mental health issues.

Australian firm Medibio’s technology derives mental health biomarkers from data gathered by wearables that measure aspects like heart rate and sleep patterns.

The company has used its technology to aid in screening, diagnosing, monitoring and management of a number of mental health issues, including depression, anxiety, and post-traumatic stress disorder (PTSD).

The new partnership will apply Medibio’s technology to existing clinical data for Otsuka’s Abilify in the hope that specific mental health biomarkers can be identified. This data can then be fed into future Abilify trials and the development of other drugs to improve their efficacy.

“We are excited about working with Otsuka, a recognised worldwide leader in treatments for serious mental illness, to advance our mutual understanding of the biology that underpins mental illness, with the goal of improving outcomes,” says Medibio CEO and managing director Jack Cosentino.

The new deal with Medibio continues Otsuka’s interest in digital health collaborations for its lead candidate.

In 2015, the company most notably filed a ‘digital pill’ version of Abilify to the FDA. The tablet itself had a small ingestible sensor embedded into it provided by medtech firm Proteus Digital Health.

The sensor would record the time the pill reached the stomach as well as collect patient metrics like rest, body angle and activity patterns. This data was to then be passed onto a wearable patch which could further be passed on to a doctor with the patient’s consent.

The idea was to improve adherence in patients taking Abilify as well as to improve clinical decision making. But despite the FDA accepting its initial filing, it later rejected the digital pill on the grounds of a lack of supporting data.


Scottish government reveals extra funding for mental health

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The Scottish government, on Mental Health Day, has revealed that it will boost spending on mental health services by £500,000.

This tops up the current fund of £1.12 million currently given to NHS 24 for the provision of looking after the nation’s mental health.

The increase in funding will go to ensuring that NHS 24, a health information and self care advice service for Scotland, can handle more calls regarding mental health. This comes as the number of people calling the service has increased rapidly in recent years.

Between 2006 and 2016, the numbers of call received by the service has risen from 38,000 to 87,000 regarding mental health. Back in May of 2017, the service revealed that it had reached the 20 million call mark from its inception 15 years ago.

Scotland, much like the rest of the UK, is struggling with growing demand on its mental health services – it suffered a rise of 8% in suicides during 2016.

Mental Health Minister Maureen Watt said to the BBC: “Building on the plans laid out in our Mental Health Strategy, this £500,000 funding package will help NHS 24 to improve their mental health services, whether online or via telephone. This is a key part of our work to intervene early, which we know can help prevent problems from worsening.”

A recent survey conducted in Scotland revealed that 40% of Scottish workers would not openly talk about any mental health issues they were facing for fear of damaging their job prospects. 42% claimed that instead of stating that they were taking leave for mental health issues, they would be more likely to suggest it was a physical ailment instead.

It is claimed that offering better mental health support to individuals within the workplace could save business £8 billion per year. This is due to the high numbers of individuals who struggle with mental health problems, as an estimated 1 in 6 individuals experience a common mental health problem.