DISTURBING report finds that 20 million American schoolchildren have been prescribed antidepressants


Image: DISTURBING report finds that 20 million American schoolchildren have been prescribed antidepressants

In many ways the world is a far more complex, difficult place to live in now than it was 20 or 30 years ago. Social media places children under increasing pressure – and at an ever decreasing age – to look perfect, have limitless “friends” and lead apparently perfect lives. Many parents work longer hours than in previous decades, leaving them with little time and energy to spend with their kids. And children are under immense pressure to perform academically and on the sports field.

In previous years, kids could generally be found playing outside with their friends or chatting to them on the phone, but modern society leaves children isolated from one another, spending more time with virtual “friends” than real-life ones. Many spend most of their time online, hardly ever venturing outside.

This toxic mix of external pressures and isolation can leave children, particularly those struggling through adolescence, feeling depressed and confused. The solution for many parents and healthcare professionals is to simply prescribe them antidepressant medications like selective serotonin reuptake inhibitors (SSRIs). This “solution” is so widely favored, in fact, that a disturbing report by the Citizens Commission on Human Rights found that around 20 million American schoolchildren have been prescribed these dangerous drugs.

Antidepressant use in children rises sharply in seven years

Antidepressant medications are, in fact, not recommended for children under the age of 18, but you would never know that if you were to judge by the way doctors hand out prescriptions for these drugs like candy.

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According to the Daily Mail, a study recently published in the European Journal of Neuropsychopharmacology, which studied antidepressant use in children under the age of 18 in five western countries, found that there was an alarming increase in the number of prescriptions for these drugs between 2005 and 2012.

In Denmark, prescriptions for children increased by 60 percent; prescription numbers soared more than 54 percent in the United Kingdom; in Germany, they rose by 49 percent; the United States saw a 26 percent increase; and there was a 17 percent increase in antidepressant prescriptions for children in the Netherlands during that period.

This is shocking because a 2016 study published in the respected British Medical Journal, which evaluated the mental health of 18,500 children prescribed antidepressant medications, found that not only are the benefits of these drugs “below what is clinically relevant” (i.e. they don’t work), but children taking them are twice as likely to exhibit suicidal or aggressive behaviors than children who do not.

The study also found that the drug manufacturers are not only aware of this fact but that they actively try to hide the risks by labeling suicidal thoughts and suicide attempts as “worsening of depression” or “emotional liability” rather than admitting that they are side effects of the medication.

“Despite what you’ve been led to believe, antidepressants have repeatedly been shown in long-term scientific studies to worsen the course of mental illness — to say nothing of the risks of liver damage, bleeding, weight gain, sexual dysfunction, and reduced cognitive function they entail,” warned holistic women’s health psychiatrist, Dr. Kelly Brogan, writing for Green Med Info. “The dirtiest little secret of all is the fact that antidepressants are among the most difficult drugs to taper from, more so than alcohol and opiates.

“While you might call it ‘going through withdrawal,’ we medical professionals have been instructed to call it ‘discontinuation syndrome,’ which can be characterized by fiercely debilitating physical and psychological reactions. Moreover, antidepressants have a well-established history of causing violent side effects, including suicide and homicide. In fact, five of the top 10 most violence-inducing drugs have been found to be antidepressants.”

This doesn’t mean that our children need to be left to struggle through depression and isolation without any help, however. Experts recommend family, individual and other therapies, lifestyle changes including exercise and dietary changes, and spending more time outdoors with family and friends as healthy, side-effect-free ways to help kids cope.

Learn more about the dangers of antidepressant drugs at Psychiatry.news.

Sources include:

GreenMedInfo.com

Independent.co.uk

DailyMail.co.uk

ScienceDaily.com

Your Antidepressants Are Ending Up in The Environment, Bathing Fish in a ‘Drug Soup’


For millions of people around the globe, antidepressants are vital medications. Unfortunately, once those pharmaceuticals have done their job inside our bodies, their biochemical effects don’t stop there.

main article image

Two researchers from the University of Portsmouth are calling for greater awareness of the risks posed by our prescriptions once they’ve been flushed into the environment, in the hope we might find ways to reduce their ecological impact.

“Our aquatic life is bathing in a soup of antidepressants,” says marine biologist Alex Ford from Portsmouth’s Institute of Marine Biology.

“Antidepressant and antianxiety medications are found everywhere, in sewage, surface water, ground water, drinking water, soil, and accumulating in wildlife tissues.”

And there’s a growing pile of evidence suggesting this ‘soup’ of antidepressants and their break-down products is taking its toll on marine life.

More frightening still are indications that it doesn’t take a high concentration for effects to appear.

“Laboratory studies are reporting changes such as how some creatures reproduce, grow, the rate at which it matures, metabolism, immunity, feeding habits, the way it moves, its colour and its behaviour,” says Ford.

Several years ago, the researcher showed how low levels of selective serotonin reuptake inhibitors such as fluoxetine – the key compound in the antidepressant Prozac – altered the behaviour of amphipod shrimp, causing them to leave sheltered spots more often and risk being preyed upon.

Working with Helena Herrera, an expert in ethical pharmacology, Ford is calling for more research into the risks and benefits of psychotropic prescriptions for the environment in addition to human health.

There’s little question that mood medications help many people deal with chronic levels of clinical depression and anxiety. What is of concern is a growing number of people are turning to pharmacological treatments, increasing levels of psychotropic drugs in the environment.

A study published in 2016 found a 26 percent increase in the use of antidepressants among children and adolescents in the US from 2005 to 2012. The UK saw a 54 percent jump during the same period.

With roughly one in ten people across the Western world on long term courses of antidepressants, this upward trend has the potential to spark an environmental catastrophe.

Without adequate measures for eliminating these chemicals from our waste, we need to ask a hard question – do all of us really need to be medicated, or should we be encouraging alternatives in the name of healthier marine ecosystems?

Swapping pills for therapy or reducing their use won’t work for everybody, but as part of a multipronged approach it could help keep a cap on that growing concentration of psychotropic waste.

Disposal programmes that are tasked with collecting unused medications from patients are already active in many parts of the world, yet vary in their popularity. Improved education could make a significant difference there as well.

“Could educating the medical profession help improve the utility of take back programmes and patient behaviour with regard to drug waste?” the researchers ask.

They’re confident that even small steps would make a big difference.

Other contributions to a solution could include pharmacological companies themselves stepping up and taking a leading role in a ‘cradle-to-grave’ strategy for managing the journey beyond a medication’s delivery.

UK waste management services could also upgrade their infrastructure to reduce the levels of synthetic oestrogens in waste water, they suggest.

“These substances are not currently covered by existing regulations with regards to sewage management, and analytical methods for detection are just now becoming available,” the researchers write.

However we manage it, it’s clear that action is needed, and it’s a problem we can all do something about.

Getting a prescription to antidepressants is a big step forward for many people with a life-changing disorder. Sadly, it means our waterways and estuaries are getting a prescription as well.

Nobody can agree about antidepressants. Here’s what you need to know


For some they are lifesavers, for others ineffective and even addictive. Our special report looks at why even experts disagree on antidepressants, and what the real truth is

pill

Sabine Scheckel/Getty

“IT WAS a year of very bad things,” says Suzy Barber, who lives in London. In 2006, her brother took his own life and a close friend died from cancer. Barber lost her job as a journalist and her freelance work gradually dwindled. With not enough to occupy her, she dwelt on tiny problems. “Everything seemed so monumental,” she says.

Barber became mired in despair and self-loathing. “You can’t motivate yourself to do anything, so you’re unproductive. That manifests in you hating yourself more. You feel like you’re constantly teetering on the edge of a massive drop.”

Eventually, Barber accepted her doctor’s advice and started on antidepressants. Within six weeks, she was on the road to recovery. Counselling helped, but “the pills kicked in”, she says. “Maybe they saved my life.”

Global antidepressant use is soaring. Stories such as Barber’s make a compelling case that the drugs can be helpful. Yet it seems barely a month goes by without them being dismissed in the media as “happy pills” that get people “hooked” or turn them into zombies. Experts, meanwhile, disagree over whether the drugs genuinely have the biochemical effects claimed for them and debate rages about side effects, withdrawal symptoms and the possibility of addiction. So what should we believe – and who, if anyone, should be taking these pills?

Depression is often seen as a modern malaise, but it has always been with us, just under different names: melancholia, nervous breakdown or sometimes just “nerves”. For a long time, doctors could do little to help, but by the 1950s, the first medicines emerged. Prime among them were so-called tricyclic antidepressants. They were less than ideal, causing side effects such as weight gain and drowsiness. Giving them to people at suicide risk was itself a risk, as it didn’t take many pills to cause a fatal overdose. They were generally reserved for the most severe cases.

Things changed with the launch of Prozac in 1988. It was the first of a class of drugs known as selective serotonin reuptake inhibitors (SSRIs) that are said to work by boosting levels of a brain-signalling molecule called serotonin. Prozac was safer than its predecessors, less likely to cause side effects, and had to be taken just once a day. Sales quickly took off. In 1990, the pale green and white capsules made the cover of Newsweek. In his 1993 book Listening to Prozac, psychiatrist Peter Kramer even said they made his patients feel “better than normal”.

With Prozac’s success, other firms raced to develop more SSRIs, as well as drugs known as SNRIs that boost noradrenaline, another brain chemical. The number of conditions they were used for grew to include anxiety, panic attacks and obsessive-compulsive disorder.

Today, around 40 antidepressants are available, and they are among the most commonly prescribed drugs in many Western countries. Between 2000 and 2015, prescriptions increased in all 29 countries surveyed by the Organisation for Economic Co-operation and Development, on average doubling. According to the UK’s National Health Service (NHS), in 2015-2016, by some measures, as many as one in 10 adults in England were prescribed the drugs. The National Center for Health Statistics cites similar figures in the US.

prozac art installation

The world’s most-prescribed antidepressant has even inspired art installations

For some, the rise in antidepressant use is a welcome sign that the stigma surrounding mental health problems is in decline and more people are prepared to seek medical help. But not everyone accepts this narrative.

For a start, there have long been holes in the “chemical imbalance” theory, the idea that SSRIs work by fixing a lack of serotonin. The drugs do raise serotonin levels in the junctions between brain cells, but there is no consistent evidence that people with depression have less serotonin than others. There is even less evidence that SNRIs work by correcting an imbalance of noradrenaline.

Mysterious mechanism

That does not mean the drugs don’t work. Even most sceptics agree that antidepressants have psychological effects. These vary from person to person, but many describe a slight dampening of their emotions – a feeling of being chilled out. “It was just enough to take the edge away,” says Barber, who was prescribed an SSRI called citalopram. “That was what I needed at the time: everything to be a little bit flatter.”

Yet strangely, although the flattening happens quickly, within days or sometimes even hours of the first dose, depression itself usually does not abate until several weeks later, as if it takes time for people to relearn their old ways. One alternative explanation for how antidepressants work is that they boost the growth of new brain cells, which takes weeks.

On top of their mysterious mechanism, there is also controversy about just how many people benefit from antidepressants. That stems from work by Irving Kirsch, a psychologist at Harvard Medical School, beginning in the 1990s. He says he initially had nothing against antidepressants and sometimes recommended them to his psychotherapy clients.

Kirsch was studying the placebo effect, the mysterious improvement in some cases of illness, apparently by the power of mind over matter, after people take medicines known not to work. Antidepressants had been known for decades to show a much bigger placebo effect than other commonly prescribed medicines such as antibiotics – a case of mind over mind. When Kirsch and his colleagues pulled together results from many different trials that compared antidepressants with placebo tablets, they found that about a third of people taking placebo pills showed a significant improvement. This was as expected. Aside from the classic placebo response, it could have been due to things such as the extra time spent talking to doctors as part of the trial, or just spontaneous recoveries.

What was surprising was how people on antidepressants were only a little more likely to get better than those on the placebos. Hard as it is to swallow, this suggests that when people like Barber feel better after starting medication, it is not necessarily down to the pills’ biochemical effects on the brain.

Kirsch’s results caused uproar. “It’s been very controversial,” he says. They have since been reproduced in several other analyses, by his group and others. As a result, some clinical guidelines now recommend medication only for those with severe depression, where meta-analyses suggest a bigger benefit. For mild to moderate depression, UK doctors were told in 2009 to offer talking therapies to begin with (see “Other ways to treat depression”). But these are no panacea, and the wait for such treatment on the NHS can be many months. In practice, pills are often still the first resort in the UK and many other places.

Other ways to treat depression

For mild or moderate depression, UK, Australian and New Zealand guidelines among others recommend talking therapies such as cognitive behavioural therapy. Lifestyle changes can also help, including cutting down on alcohol, establishing regular sleep patterns and being physically more active. “There’s a lack of public understanding of the positive impact of good physical exercise,” says Nick Stafford of Midlands Partnership NHS Foundation Trust, UK.

For people with severe depression, the last resort is electroconvulsive therapy: subjecting the brain to electric shocks under anaesthesia. This is thought to be quite effective, but often causes memory loss.

New medicines based on ketamine may become available in the next few years. Although developed as an anaesthetic and snorted as a recreational drug, doctors have found that a single injection can alleviate severe depression, with benefits lasting for many months.

A recent development suggested that the criticisms of antidepressants were misplaced after all. In April, The Lancet published the biggest analysis to date, led by psychiatrist Andrea Cipriani at the University of Oxford. It covered 21 of the commonest antidepressants and encompassed more than 500 international trials, both published and unpublished, with over 100,000 participants. For each drug, people were more likely to benefit from antidepressants than dummy pills. The size of the effect varied, but most medicines were about 50 per cent more likely to produce a response than placebos.

The results were widely reported as “putting to bed” the controversy. Far from it. Kirsch, for instance, says the authors used a misleading measure of the drugs’ efficacy. Depression is usually assessed using a questionnaire that gives a number on the Hamilton Depression Scale between 0 and 52, rising with severity. The antidepressants did indeed increase people’s chance of a positive response. Yet Kirsch points out that those who took the drugs showed an average reduction on the Hamilton scale that was only about two points greater than that of those taking the placebo tablets. “It’s an extremely small effect size,” he says.

But at least there is a measurable effect, counters John Ioannidis of Stanford University in California, one of those who carried out the Lancet analysis. “You can see that as the glass is half empty or half full.”

On the up

And the average effect hides great variation in responses, says James Warner, a psychiatrist at Imperial College London. “Looking at mean responses irons out those that don’t respond at all and those that respond quite well.”

As with all medicines, potential benefits must be weighed against risks. The great variation in people’s response is also true for the side effects. Although generally less unpleasant than those caused by older antidepressants, the unwanted effects of newer pills such as Prozac include insomnia, agitation and loss of libido. They can also trigger more alarming reactions, such as violent or suicidal impulses, but this is thought to be rare. Even David Healy, a psychiatrist at the Hergest Unit in Bangor, UK, who helped to publicise these effects, still recommends the drugs to patients who are severely anxious or who have responded well to the medicines in past depressive episodes. “People need to realise they come with risks,” he says. “But they can be useful.”

Old and depressed

Many doctors think that antidepressants are worth a try, and they can always be stopped if side effects get too bad. “Every clinician will balance the risk-benefit equation and discuss that with the patient,” says Warner.

But it might not be that simple. Some antidepressant users report reactions on stopping the medication, including anxiety, insomnia and sudden bouts of dizziness, lasting for months. It’s not known what might be causing these “withdrawal symptoms”, but animals given SSRIs for an extended period respond by reducing the number of serotonin receptors in their brain, thus keeping serotonin levels constant. Plausibly, when people stop taking SSRIs, serotonin signalling falls too low, triggering the symptoms.

The general advice is to reduce antidepressant dose slowly. But many doctors don’t know just how gradually to do it and some antidepressants are not available in small enough doses to allow this, says James Moore, who started a campaign called Let’s Talk Withdrawal to help those like him who have been affected. Moore says many people contacting his website have experienced what seem to be classic withdrawal symptoms and yet were apparently told that this must be a return of their original condition.

After the Lancet meta-analysis came out, Wendy Burn, the president of the UK’s Royal College of Psychiatrists, wrote a letter to The Times newspaper to defend antidepressants. She wrote that for most people, withdrawal symptoms last no more than two weeks.

What is clinical depression?

Ups and downs are a part of normal life, so when does sadness become an illness? Doctors define depression as persistent low mood, plus feelings of doubt and self-loathing, lasting for more than two weeks. “People lack energy all of the time and can’t enjoy the things they used to,” says Nick Stafford of the Midlands Partnership NHS Foundation Trust, UK.

These psychological symptoms are often coupled with physical ones such as changes in appetite or trouble sleeping. It is common for people to wake up early in the morning with miserable thoughts whirling around in their mind, says Stafford.

This has inflamed critics. “By stating that withdrawal isn’t a problem, they may have been responsible for encouraging more people to expose themselves to unnecessary harm,” says Sami Timimi, a psychiatrist in Lincoln, UK. Along with 29 others, Timimi wrote to the college’s complaints committee to say that the letter contradicted a survey of more than 800 people conducted by the college itself. This found that withdrawal symptoms generally last for up to six weeks and that a quarter of people have anxiety lasting more than three months. The college responded that the survey results could be misleading as participants were self-selecting and people might be more likely to take part if they have had bad experiences. It has taken down the results from its website.

The truth is we don’t know how common long-lasting withdrawal symptoms are. The trials conducted by drug manufacturers to get their medicines on the market are designed to investigate effectiveness and side effects that arise in the course of treatment, not what happens afterwards.

Not everyone experiences withdrawal symptoms. Barber didn’t, for instance. Another user, Tom, whose work problems led to depression and anxiety, experienced nightmares and dizziness for a month after he stopped taking the drugs – yet he feels overall they were worth it. Moore is at the other extreme: he has been trying to come off medication for over a year, and wishes that first pill had never passed his lips.

The problem of withdrawal symptoms lies behind claims that antidepressants are addictive. This is hard to evaluate: we don’t know how common prolonged withdrawal symptoms are, and there is also no universally accepted definition of addiction. Cipriani is among those who believe that antidepressants cannot be addictive because users don’t seek an ever-increasing dose to get the same effect. But DSM-5, the bible of US psychiatry, defines someone as addicted to a substance if they have difficulty stopping its use and take it for longer than intended. That would apply to some with bad withdrawal symptoms.

Gender imbalance

One option is to let people themselves define whether or not they are addicted, says John Read, a psychologist at the University of East London, and a signatory to the complaint letter. Read has published a survey of more than 1800 current or former antidepressant users from New Zealand. About a quarter felt their medication was addictive.

An inquiry by Public Health England into dependence on prescription drugs, due to report early next year, may shed light on the issue. The review will include medicines widely accepted as addictive, such as opioid painkillers, as well as antidepressants – to the displeasure of some psychiatrists. Meanwhile, also in the UK, trouble is brewing over the evidence used to assess the effectiveness of drugs and other treatments for depression (see “Flawed evidence?”).

“Trials are not designed to learn what happens when you stop taking the drug”

With the science so unsettled, antidepressants will continue to be one of the most divisive types of drug in use today. Could it be that both sides have a point? As Moore sees it, although these medicines do help some people, they carry risks that mean they are best avoided if possible for those with less severe illness. Indeed, many psychiatrists accept that they are still being prescribed too freely for people at the milder end of the spectrum, who should first be advised to try talking therapies and lifestyle changes.

At the same time, though, some people with severe illness who might really benefit from antidepressants are put off taking them because of the lingering stigma. “Some think taking medication for a mental health problem is a sign of weakness or a character flaw,” says Nick Stafford, a psychiatrist at Midlands Partnership NHS Foundation Trust, UK. Cipriani agrees. “If you give the message that antidepressants are like a placebo, the message is that depression is not real, it’s all in the mind,” he says. “But it’s an illness.”

“I’m not trying to get the drugs banned – they have a valid role,” says Moore. But family doctors as well as psychiatrists need to discuss the potential for harm more, he says. “I want patients to hear all the facts when they have that initial discussion about whether an antidepressant is right for them. At the moment, that’s not happening.”

Flawed evidence?

by Moya Sarner

It isn’t often that psychiatrists, therapists, doctors, researchers and patients agree. But in June, a coalition of professional bodies and mental health charities put out a joint statement calling on the UK’s National Institute for Health and Care Excellence (NICE) to rewrite its draft guidance for treating depression.

The current advice was published in 2009, and the latest draft wouldn’t change the status quo on recommended treatments: mainly drugs and cognitive behavioural therapy, including online or over the phone. But coalition members contend that the guidance is flawed.

Discounted Evidence

For a start, instead of referring to mild, moderate and severe depression, NICE proposes new categories, including less severe depression and more severe depression. These don’t match clinicians’ or patients’ experiences, says Felicitas Rost, president of the UK Society for Psychotherapy Research and leader of the coalition. “No one else has come up with these distinctions. This system is not reliable, has not been validated by the research community and will be completely out of step with American and European guidelines,” she says.

But the coalition’s biggest criticism is for NICE’s approach to evidence. It only considers randomised controlled trials, the “gold standard” of medical evidence in which one group of participants is given an active ingredient and another group a placebo, so any changes can be attributed to the active ingredient.

This approach works for antidepressants, even if the degree to which it shows significant benefit from the drugs is disputed. But it doesn’t work for psychotherapy. “If one therapist has five patients, the relationship with each of them is different, whereas the antidepressant doesn’t change,” says Rost. She argues that other lines of evidence must be used when assessing psychological therapies. These include recovery rates from depression for those already receiving treatment, which is routinely collected by mental health teams across the country, and studies that ask people what treatments they have and haven’t found helpful, says Rost. Susan McPherson at the University of Essex, who co-wrote the coalition statement, found that NICE excluded 93 studies that gave voice to 2500-plus patients.

Another criticism is that, unlike guidelines for treating physical conditions, no research into the longer-term impact of treatments for depression is included in the latest proposal. UK National Health Service bodies are required by law to give equal priority to mental and physical health. But whereas the guidance on treating epilepsy, for example, includes data that was gathered up to 10 years after treatment, for depression it is less than a year. “For me, this is the most important point,” says Rost. “Depression is a long-term condition, so we need to show in our studies if the benefit of a treatment is sustained.” The worry is that by excluding such evidence, the guidance skews treatment towards medication and shorter forms of psychological therapies.

Approached for a response, NICE refused to comment on specifics, saying that “the committee are in the process of updating the guidance”. The body took the unusual step of holding a second consultation in July. The final version of the advice is due to be published soon.

Antidepressants Cause Severe Withdrawal Symptoms, New Study Reveals


Antidepressants Cause Severe Withdrawal Symptoms like “Hallucination”, “Mania” and “Anxiety”, New Study Reveals

New research reveals severe withdrawal symptoms in over half of those who discontinue antidepressant drugs, including lasting and even permanent damage.

A concerning new study published in the journal Addictive Behavior and titled “A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based?” reveals that antidepressants are far more addictive and harmful than previously assumed, and vindicates the long-time activism on this issue spearheaded by American psychiatrists like Kelly Brogan, MD and Peter Breggin, MD.

Highlights from the paper are as follows:

  • More than half (56%) of people who attempt to come off antidepressants experience withdrawal effects.
  • Nearly half (46%) of people experiencing withdrawal effects describe them as severe.
  • It is not uncommon for the withdrawal effects to last for several weeks or months.
  • Current UK and USA Guidelines underestimate the severity and duration of antidepressant withdrawal, with significant clinical implications.

This study aimed to assess the veracity of the the U.K.’s current National Institute for Health and Care Excellence and the American Psychiatric Association’s depression guidelines which state that withdrawal reactions from antidepressants are ‘self-limiting’ (i.e. typically resolving between 1 and 2 weeks).

In order to accomplish this goal the systematic review used the following methods:

“A systematic literature review was undertaken to ascertain the incidence, severity and duration of antidepressant withdrawal reactions. We identified 23 relevant studies, with diverse methodologies and sample sizes.”

The results were reported as follows:

“Withdrawal incidence rates from 14 studies ranged from 27% to 86% with a weighted average of 56%. Four large studies of severity produced a weighted average of 46% of those experiencing antidepressant withdrawal effects endorsing the most extreme severity rating on offer. Seven of the ten very diverse studies providing data on duration contradict the UK and USA withdrawal Guidelines in that they found that a significant proportion of people who experience withdrawal do so for more than two weeks, and that it is not uncommon for people to experience withdrawal for several months.”

Side effects were wide-ranging, lasting several months or longer (including permanent dysfunction), such as: 

“Typical AD withdrawal reactions include increased anxiety, flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. Dizziness, electric shock-like sensations, brain zaps, diarrhoea, headaches, muscle spasms and tremors, agitation, hallucinations, confusion, malaise, sweating and irritability are also reported (Warner, Bobo, Warner, Reid, & Rachal, 2006, Healy, 2012). Although the aforementioned symptoms are the most common physical symptoms, there is also evidence that AD withdrawal can induce mania and hypomania, (Goldstein et al., 1999; Naryan & Haddad, 2011) emotional blunting and an inability to cry, (HolguinLew & Bell, 2013) long-term or even permanent sexual dysfunction (Csoka & Shipko, 2006).”

The study concluded:

“We recommend that U.K. and U.S.A. guidelines on antidepressant withdrawal be urgently updated as they are clearly at variance with the evidence on the incidence, severity and duration of antidepressant withdrawal, and are probably leading to the widespread misdiagnosing of withdrawal, the consequent lengthening of antidepressant use, much unnecessary antidepressant prescribing and higher rates of antidepressant prescriptions overall. We also recommend that prescribers fully inform patients about the possibility of withdrawal effects.”

The researchers also noted that the rising numbers of antidepressant prescriptions used throughout the world may be fueled by the antidepressant drug withdrawal side effects themselves:

“As the lengthening duration of AD use has fuelled rising AD prescriptions over the same time period, we must understand the drivers of such lengthening use. The evidence set out suggests that lengthening use may be partly rooted in the underestimation of the incidence, severity and duration of AD withdrawal reactions, leading to many withdrawal reactions being misdiagnosed, for example, as relapse (with drugs being reinstated as a consequence) or as failure to respond to treatment (with either new drugs being tried and/or dosages increased). This issue is pressing as long-term AD use is associated with increased severe side-effects, increased risk of weight gain, the impairment of patients’ autonomy and resilience (increasing their dependence on medical help), worsening outcomes for some patients, greater relapse rates, increased mortality and the development of neurodegenerative diseases, such as dementia.”

The concerning implications of this study to millions around the world who are on antidepressants were immediately recognized by the media, as evidenced by mainstream reporting on the topic with the following headlines:

Antidepressants, Psychotherapy May Help Ease Irritable Bowel Syndrome


People struggling with irritable bowel syndrome (IBS) might feel better with antidepressants or psychotherapy, a recent study suggests.

While in some people, IBS improves with customized diets, this approach doesn’t help everyone and some emerging research suggests that the condition may also be influenced by processes in the brain.

For the current analysis, researchers examined data from 53 trials that compared the effects of antidepressants or psychotherapy, either alone or in combination, versus placebo treatments or usual care.

Rates of “no relief” were highest with placebo treatments. People were 34% less likely to have no relief from antidepressants and 31% less likely to get no relief from psychotherapy, the study found.

“One component of IBS is increased sensitivity to the functions of the bowels; simply summarized, this means either the nerves taking messages from the bowel to the brain are more sensitive or that the brain is more attentive or reacts in a more emotional manner to the normal messages arising in the bowel, or both,” said Dr. Michael Camilleri, a researcher at the Mayo Clinic College of Medicine and Science in Rochester, Minnesota, who wasn’t involved in the current study.

“Since there are really no medications to reduce the nerve sensitivity, some doctors give medications that modulate the function of the brain in the hope that this approach will reduce the ability to sense or emotionally react to the signals or messages arriving from the bowels,” Camilleri said by email.

Psychiatric conditions including depression, anxiety, and somatization are common among people with IBS, researchers noted online September 3 in the American Journal of Gastroenterology.

Although the use of antidepressants is common among IBS patients, psychotherapy is not, the study authors note.

One limitation of the current study is that the smaller studies used in the analysis had a wide variety of designs and methods for testing the success of treatment, researchers note. Another drawback is that these studies weren’t designed to prove how antidepressants or psychotherapy might directly improve IBS symptoms.

Still, a psychological evaluation may make sense for IBS patients because it’s possible their symptoms might be a byproduct of untreated depression, said Dr. Agnieszka Kulak-Bejda, a psychiatry researcher at the Medical University of Białystok in Poland who wasn’t involved in the study.

Antidepressants may work better for certain types of IBS, and the study findings also suggest that the type of medication may matter, Kulak-Bejda said by email.

Tricyclic antidepressants were more effective at relieving global symptoms of IBS, the analysis found. But selective serotonin reuptake inhibitors (SSRIs) were better than a placebo for easing symptoms like pain and bloating and improving quality of life.

“The decision to use antidepressants as a form of therapy should be taken individually,” Kulak-Bejda said. “The decision should be made after considering all the pros and cons.”

Antidepressants for the treatment of depression in people with cancer.


BACKGROUND: Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results.

OBJECTIVES: To assess the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage).

SEARCH METHODS: We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 6), MEDLINE Ovid (1946 to June week 4 2017), Embase Ovid (1980 to 2017 week 27) and PsycINFO Ovid (1987 to July week 4 2017). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials.

SELECTION CRITERIA: We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis).

DATA COLLECTION AND ANALYSIS: Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into Review Manager 5 using a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by Cochrane.

MAIN RESULTS: We retrieved a total of 10 studies (885 participants), seven of which contributed to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update we included one additional unpublished study. These new data contributed to the secondary analysis, while the results of the primary analysis remained unchanged.For acute-phase treatment response (6 to 12 weeks), we found no difference between antidepressants as a class and placebo on symptoms of depression measured both as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants; very low certainty evidence) and as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants; very low certainty evidence). No trials reported data on follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, showing no difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants; very low certainty evidence). No clear evidence of a beneficial effect of antidepressants versus either placebo or other antidepressants emerged from our analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low certainty evidence). In terms of dropouts due to any cause, we found no difference between antidepressants as a class compared with placebo (RR 0.85, 95% CI 0.52 to 1.38, seven RCTs, 479 participants; very low certainty evidence), and between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the certainty (quality) of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity.

AUTHORS’ CONCLUSIONS: Despite the impact of depression on people with cancer, the available studies were very few and of low quality. This review found very low certainty evidence for the effects of these drugs compared with placebo. On the basis of these results, clear implications for practice cannot be deduced. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent to prescribe may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. To better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.

 

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Recent Study Confirms That Antidepressants Increase Suicide Risk


Robin Williams, Chris Cornell, and Chester Bennington all revealed details of their struggles with depression and anxiety before they made the tragic decisions to end their lives. You’re probably not surprised that people diagnosed with a psychiatric disorder, such as depression or anxiety, have an increased risk of suicide; in fact, a recent study estimates that 80% of people who attempt suicide have a psychiatric diagnosis associated with suicidal ideation. The startling news comes from the science that supports the causal role of antidepressants in the actual completion of suicide.

If depression leads to suicide and antidepressants like SSRIs resolve depression, we could decrease suicide rates by increasing the number of antidepressant prescriptions, right? That’s the pharmaceutical argument for medicating people who are “at risk”.

Yet, the evidence reveals some inconvenient truths, demonstrating that antidepressants actually increase the risk of suicide. Furthermore, just as the serotonin model of depression has never been scientifically validated, there is no evidence that antidepressants meaningfully and statistically significantly resolve depression – but, instead, we are confronting a growing signal of harm, including live-streamed suicides and school shootings committed by those recently prescribed. And a new study from Sweden that examines antidepressants in the context of suicide suggests that antidepressants are pushing people towards, not away from, suicide.

Swedish researchers analyzed data in a timespan in which antidepressant prescriptions rose steadily; the percentage of young women who were prescribed antidepressants increased from 1.4% to 5%. Approximately 500 young women committed suicide during this time period, and because toxicological analyses were performed postmortem, researchers could determine if these women were on antidepressants at the time that they made the decision to end their lives.

antidepressant-prescriptions-increased
From 1999 to 2013, antidepressant prescriptions increased 270%. In 2013, about 5% of Swedish young women (36,141) were prescribed antidepressants.

If antidepressants indeed resolve depression and prevent suicide, those who committed suicide, would be the unmedicated ones right? Also, suicide rates would decrease as antidepressant prescriptions increased.

Yet, researchers found the opposite. As antidepressant prescriptions increased 270% over 15 years, suicide rates also increased. Strikingly, more than half of the young women who committed suicide (52%) were prescribed antidepressants within a year of committing suicide. And antidepressants were detected in 41% of the women who committed suicide, showing that they were under the influence of antidepressants at the time of death. In the remaining subjects, it is also important to know whether they had recently discontinued psychotropic medication. As many who have done so would tell you, abrupt (or sometimes even cautious) tapering of medication can lead to suicidality and homicidality with associated impulsivity (long after the medication itself is undetectable).

We are a culture that believes that force is necessary for change and progress (rather than natural momentum and emergent processes). But maybe we shouldn’t be surprised when we learn that throwing more of the same failed medicine at the very problem created by the failed medicine – well, it doesn’t actually work. Herein lies the thinly-veiled agenda of the industry – use the shortcomings of the intervention (in this case, continued and worsened depressive symptoms) to justify further interventions (more medications for all). This is like calling for more and more barricades to cover up any visual evidence of a forest fire while the fire blazes behind the facade. What is needed, at the first sign of risk outweighing benefit, is true informed consent – and thankfully, each and every prospective patient can now be empowered with a fuller version of the truth than they might receive from media, the government, or their prescribing doctor.

How long should you stay on antidepressants? 


As many as 5.4 million people in the UK may be taking pills to help with anxiety and depression, but does that mean they are hooked?

Doctor in discussion with patient
It’s important to discuss a plan for coming off antidepressants with your doctor. 

According to reports last week, hundreds of thousands of people are hooked on prescription drugs for not only depression but also pain and anxiety. The Daily Mail quoted a recent report from the all party parliamentary group for prescribed drug dependence, saying that in 2013 about 11% of women and 6% of men were on antidepressants – 5.4 million people nationally.

But are they really hooked? The Royal College of Psychiatry says that antidepressants are not addictive, on the grounds that you do not have to increase your dose to get the same effect or get cravings when you stop the drug. But the college’s own survey of 817 people found that 63% had withdrawal symptoms after stopping antidepressants – mostly they were on SSRIs (the most commonly prescribed antidepressants).

The solution

The symptoms of withdrawal – stomach upsets, flu-like symptoms, anxiety, dizziness, nightmares and electric shocks to the head – can last for two months. Dr James Davies, an academic in social and medical anthropology at the University of Roehampton and member of the all parliamentary group says that people on antidepressants can certainly feel dependent on their drug. “Dependence can be physical or psychological,” he says. “People may feel they are only better because they take the drug.”

In a letter to the BMJ last year, Prof Peter C Gøtzsche of the Nordic Cochrane Centre in Denmark said that half of people on antidepressants become addicted. Out of 260,322 people in Finland who were taking an antidepressant in 2008, 45% were still on them five years later.

When you stop antidepressants should be the result of a discussion between you and your doctor – it is an individual decision and depends on how long and how severely you have been depressed. A precipitating cause may have gone, or talking therapy may have helped. But you should never stop taking them suddenly because the side-effects can be horrible. Instead, it is recommended that you taper your dose by a quarter every four to six weeks.

Psychiatrists suggest staying on the drug for six months to a year after you feel better. Your response should be checked regularly – at three weeks and then again at three to six monthly intervals. Doctors can sometimes confuse withdrawal symptoms with a return of depression, and restart the drug. Gøtzsche warns that this can keep people trapped on antidepressants for life. If the symptoms occur rapidly after stopping the drug, and stop very shortly after restarting it, then it is likely to be because of drug withdrawal. GPs often advise coming off antidepressants at the start of summer, as it feels a more optimistic time than the middle of winter.

Source:www.theguardian.com

Neurometabolic Disorders Could Contribute to Depression


Impairments in the production of neurotransmitters may lead to depression in some patients, preliminary results show, opening new avenues for research..

Deficiencies in key compounds that help the body make neurotransmitters may contribute to the intractability of depression in some people.

In 2002, psychiatrist Lisa Pan, a depression and suicide prevention researcher at the University of Pittsburgh Medical Center (UPMC), met Kyle, a 19-year-old suffering from depression (name altered to preserve confidentiality). He was among the estimated 15 percent of depression patients in the U.S. for whom treatments such as antidepressants or therapy do not help. He “had been through every available treatment” including electroconvulsive therapy, but nothing worked, Pan recalls. “At one time, he was on 17 medications simultaneously.” The teenager had attempted suicide, and doctors determined that he was at risk for similar episodes. The next step for him would be state hospitalization.

Having exhausted conventional treatment options, Pan went off script. She enlisted a colleague at UPMC, geneticist David Finegold, to run tests on Kyle’s neurometabolic system, which supplies nutrients necessary to maintain neurons with a healthy supply of neurotransmitters. The tests revealed that Kyle underproduced tetrahydrobiopterin (BH4), a necessary cofactor for enzymes involved in making serotonin, dopamine, and other compounds that modulate emotions and mood. Pan gave him sapropterin, a synthetic form of BH4, to bring his system back into balance. “It took some time, but he got better,” she says. Kyle left the hospital and went on to graduate from college.

“We felt like we might be onto something,” Pan says. She began exploring the possibility that metabolic imbalances affected others for whom standard depression treatment had failed. She and her colleagues conducted an array of blood, urine, and cerebrospinal fluid tests in 33 such individuals, each of whom had shown negligible response to at least three different maximum-dose depression medications administered for six weeks or more. Ranging from teenagers to middle-age adults, the group included some who also suffered post-traumatic stress disorder (PTSD), anxiety, or attention deficit hyperactivity disorder (ADHD).

When the tests came back, about a third of the patients showed a deficiency in the levels of folate in their spinal fluid, another key compound for producing a variety of neurotransmitters. Taking a folate supplement to correct this imbalance improved patients’ depression symptoms, lowering their scores on a questionnaire for suicidal thinking and another for mental and physical signs of depression. And Pan says that as each patient continued to take the supplement, their symptoms continued to improve (Am J Psych, appiajp201615111500, 2016).

Since the publication of these results, “we have gotten hundreds of phone calls from people just asking for help,” she says. As Pan returns these calls, she explains that her findings are preliminary. Her study documents relatively few individual treatment outcomes and is not a formal clinical trial. As the study continues and expands to include more patients, Pan and her colleagues will work to identify the cause of folate deficiency and to investigate whether folate supplementation could become a standard treatment. But these results suggest that treating an underlying neurometabolic imbalance can alleviate depression at least in some cases, which should open a door to new research. Receiving the influx of phone calls “makes me want to work more,” Pan says.

Characterizing depression in broad strokes is almost impossible, cautions David Brent, a former advisor to Pan and coauthor on the study. “There are a lot of people who look the same that probably have very different causes” of depression. Other psychological conditions, including PTSD and anxiety, frequently coincide with and complicate the disorder. “We’re really just at the beginning of extricating” these interacting factors, Pan says, and at this stage, developing solutions that can be standardized for treating many people is difficult.

Even so, Finegold notes that preliminary studies like this one have a way of offering hope to people who have not found a successful depression treatment. He, too, receives phone calls from people living with depression, and some express their gratitude simply to know that new aspects of the problem are being explored.

One avenue of Pan’s further exploration is to search for genetic markers associated with neurometabolic imbalances. Ideally, genetic testing could be used alongside traditional clinical evaluations to provide physicians with as much patient information as possible, says coauthor David Peters, a geneticist at UPMC. Testing spinal fluid is invasive and time-consuming; a quick DNA swab is much more practical, and Peters says incorporating genetic testing is a “very exciting prospect.”

Every six months or so, Pan checks in with Kyle. Having graduated college, he now works in environmental science, and the only medication he takes is sapropterin. In a statement he authorized her to share, Kyle says, “It’s safe to say that I owe my life to the successful diagnosis.”

Most Antidepressants Ineffective for Kids With Depression


With the possible exception of fluoxetine (multiple brands), the vast majority of antidepressants are ineffective, and some may even be unsafe, for use in children and teens with major depressive disorder (MDD), new research shows.

“The only treatment that is evidence-based is fluoxetine,” lead researcher Andrea Cipriani, PhD, associate professor, Department of Psychiatry, University of Oxford, United Kingdom, told Medscape Medical News.

However, Dr Cipriani stressed that this applies to children with moderate to severe depression for whom psychotherapy or other nonpharmacologic interventions have been tried without success or in situations in which such interventions are unavailable.

“And it doesn’t mean that if I have a patient who is responding to escitalopram [Lexapro, Forest Laboratories, Inc], that I should stop escitalopram and put that patient on fluoxetine, because these are average data for an average patient.”

Dr Cipriani also stressed that the use of antidepressants in children is “not cookbook medicine. Everything has to be individualized to the specific patient.”

The findings were published online June 8 in the Lancet

One Drug Better Than Placebo

MDD is one of the most common mental disorders in children and adolescents, the investigators note. However, whether to use pharmacologic agents in this population and which drugs are optimal remains controversial.
To compare and rank antidepressants and placebo for the treatment of MDD in young patients, the researchers conducted a meta-analysis to identify both direct and indirect evidence from relevant trials.

They searched for double-blind, randomized controlled trials involving the use of antidepressants for the acute treatment of MDD in children and adolescents through May 31, 2015. The analysis included 34 trials in which 5260 patients were enrolled; 14 antidepressants were assessed for efficacy and tolerability.

The mean study sample size was 159 participants; the mean age of the patients was 13.6 years; and the median duration of acute treatment was 8 weeks. About two thirds of the trials (65%) were funded by pharmaceutical companies.

In terms of study quality, 29% of the trials were rated as having a high risk for bias, 59% as having a moderate risk, and 12% as having a low risk.

The primary outcome was mean overall change in depressive symptoms and the proportion of patients who discontinued treatment due to any adverse events. To assess change in depressive symptoms, the investigators extracted a score from scales used in the studies. These scales included the Children’s Depression Rating Scale Revised, the Beck Depression Inventory, and the Children’s Depression Inventory.

Secondary outcomes included response rate, all-cause discontinuation, and suicidal behavior and ideation. Response rate was determined on the basis of the proportion of patients who achieved a reduction of 50% or more in depressive symptoms or whose scores on the Clinical Global Impression scale were much improved or very much improved.

Suicidality Risk

The researchers performed a “network” meta-analysis that allowed them to use indirect as well as direct evidence from the relevant trials to calculate comparisons and to rank probabilities for all treatments.

The analysis showed that in terms of efficacy, only fluoxetine was better than placebo (standardized mean difference [SMD], – 0.51; 95% credible interval [CrI], -0.99 to -0.03).

However, the authors point out that “the large credible interval and its upper limit close to the point of no difference raise the question of whether this estimate is robust enough to inform clinical practice.”

Nortriptyline (multiple brands) was significantly less effective than seven other antidepressants and placebo.

In terms of tolerability, fluoxetine was significantly better than duloxetine (Cymbalta, Eli Lilly and Company) (odds ratio [OR], 0.13; 95% CrI, 0.13 – 0.95) and imipramine (multiple brands) (OR, 0.23; 95% CrI, 0.04 – 0.78). Citalopram and paroxetine (multiple brands) were significantly better tolerated than imipramine alone (OR, 0.27 and 0.22, respectively). Imipramine was significantly less well tolerated than placebo, as was venlafaxine (multiple brands) and duloxetine.

For the most part, the results for secondary outcomes “were not materially different from, and lent support to, the findings for primary outcomes,” the authors write.

Although the current study could not comprehensively assess the risk for suicidality for all drugs, there was robust evidence suggesting a significantly increased risk for suicidality for young people given venlafaxine.

The ranking of treatments, based on cumulative probability plots and surface under the cumulative ranking curve, showed that the most effective treatment was fluoxetine (76.6%) and that the least effective was nortriptyline (3.7%). Fluoxetine also came out on top in terms of tolerability (75.7%), with imipramine coming in last (13.1%).

Advantages of Fluoxetine

Fluoxetine has a number of advantages, said Dr Cipriani. Being the first new-generation antidepressant (selective serotonin reuptake inhibitor), it has been “very well studied” and has many years of “real-world use.”

It has a long half-life, requiring a few weeks to metabolize. Because of this, missing a dose may not be a problem.

“With children, there is sometimes a problem with compliance, and if you have a drug with a very short half-life, and you don’t take it regularly, you might have withdrawal symptoms,” said Dr Cipriani.

Fluoxetine is also widely available. “It’s one of the WHO [World Health Organization] essential medicines, so it’s available everywhere, including developing countries and where there’s a refugee crisis,” said Dr Cipriani.

But it is not without disadvantages. For example, switching from fluoxetine to another medication requires a washout period, and fluoxetine can interact with other medications.

“You need to be careful if you are adding other treatments, such as antibiotics,” said Dr Cipriani.

The authors caution about clinical interpretation of the findings, owing to the uncertainty of estimates and potential bias due to selective reporting. As well, unpublished studies were not included in the analysis, and published reports may overestimate the efficacy of treatments.

In 2003, the US Food and Drug Administration (FDA) and other regulatory agencies added a black box warning to the labeling of prescription antidepressants, highlighting the possibility of suicidality in some children with MDD.

According to Dr Cipriani, there is an increased risk for suicidality, but the risk is not the same for all drugs.

Although the data gathered by the FDA are not powered to provide “clear answers,” there is “a trend” of some drugs being worse than others in terms of suicidality risk, said Dr Cipriani. “The one-size-fits-all approach is misleading.” The evidence suggests that sertraline and fluoxetine are not associated with an increased risk for suicidality, she added.

Children Not Small Adults

What is becoming clear from the research, said Dr Cipriani, is that children with MDD significantly differ from adults with depression. In children, the brain is still developing, and the clinical features of depression in children are different from those in adults.

“In adults, mainly in the elderly, depression is a lot about mood, while in young people, it’s a lot about irritability and difficulty with concentration,” said Dr Cipriani. “We tend to call it all depression and assume that the same drugs work for young people.”

A main problem is lack of knowledge about the pathophysiology of the disorder and identifying markers. “We don’t have hard outcomes to test a treatment.”

A question plaguing trials of antidepressants ― among adults as well as children ― is the high placebo response rate. According to Dr Cipriani, 50% to 60% of patients respond to an antidepressant, and about 40% respond to placebo, so the “added value” is about 10% to 15%.

The placebo response has increased over the years ― it was about 20% in the 1980s ― probably because of methodologic differences in trials. One example would be differences regarding the inclusion of less severe patients, who tend to respond more to placebo.

“But in real practice, we don’t use a placebo,” said Dr Cipriani.

Childhood depression is “a huge problem” that is growing, according to Dr Cipriani. About 3% of children younger than 12 years suffer major depression, as do 6% of persons aged 13 to 18 years.

Adverse Events Underreported

In an accompanying editorial, Jon Jureidini, MD, a child psychiatrist at the University of Adelaide and Women’s and Children’s Hospital, in Australia, writes that the evidence for the use of antidepressants in children is even weaker than the current study suggests.

“The data that the authors were working from was what were available in published articles and clinical study reports,” Dr Jureidini told Medscape Medical News. “Unless you have access to individual patient-level data, you can’t be confident that what’s in those tables and spreadsheets that these authors had to work from is actually an accurate representation of what was found.”

From his own research, Dr Jureidini has learned that “adverse events are underreported, and some outcome measures are distorted.”

One problem is that some of the clinical trials are carried out by pharmaceutical companies, which “control the flow of information,” he said.

Anther problem is that doctors are often convinced that these medicines do work, he added.

“They don’t do it deliberately, but they look at things with more of a positive lens, because they want to show that these drugs they regard as positive and valuable are in fact positive and valuable.”

What is particularly bothersome, said Dr Jureidini, is that even though these drugs are not first-line therapy, “the idea seems to be that you give the antidepressants anyway,” he said. “That’s just bad medicine; if they’re not good drugs, then you should avoid giving them.”

The use of an antidepressant in a child should usually be done only in the inpatient setting, said Dr Jureidini.

He himself has not initiated antidepressant therapy in a child more than once or twice in the past 5 years. However, it is not uncommon for him assume care for a child who is already receiving an antidepressant, “and I wouldn’t necessarily stop that.”

In the absence of available psychotherapy, there are other nondrug approaches clinicians can take to treat a child with depressive symptoms.

One is to look for a better explanation for the symptoms than to just call it major depression. “Very often, symptoms are caused by life circumstances, and sometimes those life circumstances can be addressed in a way that resolves the symptoms.”

In situations in which there is no apparent explanation for the symptoms or in which nothing can be done about them directly, Dr Jureidini suggests taking a “watchful waiting” approach, even in cases of moderate and severe depression.

It might be a matter of helping the child make sense of what they are feeling. For example, he or she might still be grieving from the loss of a beloved grandmother.

Dr Jureidini pointed out that depression usually lasts weeks, not months.

Does he think the use of antidepressants in children will disiminish significantly in response to this new study? “I hope so, but probably not.”

He sees two factors standing in the way of getting the message across ― pharmaceutical marketing, and key opinion leaders.

“In any community, particularly in North America, you find senior, often academic child psychiatrists and others who are enthusiastic prescribers of antidepressants and who will influence the prescribing pattern of many other doctors.”

He anticipates that “prominent figures” will “stand up and say either publicly or within their academic communities that this paper is misleading, that antidepressants save lives, and that we should all continue prescribing them.