Pills & ills

by Sally Blundell / 25 June, 2015
Medication for such things as ADHD and mood disorders may be having little or no effect, but a new nutritional approach is proving promising.
PillFinal

The writer, a father, sounds desperate. His 17-year-old son, diagnosed with attention deficit hyperactivity disorder (ADHD) when he was four, is finding life a “huge struggle”.

Julia Rucklidge, professor of clinical psychology at the University of Canterbury, reads out the email: “He’s had more counselling and drug treatments than any kid should have to have … nothing really helps him. He suffers from anxiousness, impulsivity, severe depression and lack of confidence.”

Rucklidge throws up her hands. “Is this as good as it gets? If [medication] is working, you should be well. It’s as if people think, if I’m on a medication and still unwell, that proves how unwell I am.”

She scrolls down through more emails: people diagnosed with schizophrenia still experiencing psychotic episodes after 20 years on medication; adults on combinations of antidepressants feeling flat, numb, disengaged; people suffering from ongoing anxiety despite a diet of prescription drugs; children with ADHD treated with Ritalin but still struggling at school. People with mental health issues, she says, “are not getting as well as we probably think they are”.

Rucklidge points to a 2003 study by US psychiatrists Martin Harrow and Thomas Jobe showing that over a 26-year period, people diagnosed with schizophrenia who had less or no long-term antipsychotic use after the initial acute phase experienced better outcomes than those who stayed on antipsychotic medication. As US National Institute of Mental Health director Tom Insel wrote at the time, “It appears that what we currently call ‘schizophrenia’ may comprise disorders with quite different trajectories.”

Another study, an eight-year analysis of 579 children with ADHD: despite access to drug treatments such as Ritalin, children on long-term medication showed no improvement in educational outcome.

Yet another, reported in a 2013 article in the Australia New Zealand Journal of Psychiatry: despite the use of antidepressants over 50 years, our recovery rates from depression are no better than they were before the advent of medication.

“Is that acceptable?” asks Rucklidge. “We have spent billions of dollars on antidepressants and there is no difference in outcome? You look at this and think, ‘What should we do?’ Do we ignore it? Do we say this is the cost of treating people with mental illness? Maybe this is acceptable.”

Psychiatrist Roger Mulder, professor of psychological medicine at the University of Otago, thinks not. “When I went into psychiatry, we had a technical paradigm: mental illness is like any other illness, so what we should do is categorise it, find the specific causes and treat it. That seemed an appealing model – it helped destigmatise mental illness, and the drugs were available.”

But this paradigm has two problems, he says. The first is that mental-heath outcomes haven’t really improved in the past 50 years. “If you look at admissions to hospital for mood disorders [such as bipolar disorder], they haven’t really changed. If you look at the outcomes of major depression in the long term, they don’t seem different. If you look at young people, rates of psychological distress appear to be increasing rather than decreasing, with younger and younger people getting psychologically distressed. And suicide rates haven’t dramatically altered.”

The second problem is that most evidence suggests general aspects of mental health care are at least as important as technical elements such as drugs and specific psychotherapies.
JuliaRucklidge

A dramatic decline in symptoms

In 1996 in rural Alberta, a widower – desperate to help his two young children diagnosed with bipolar disorder and still “very unwell” despite multiple medications – began searching for a more effective solution. He teamed up with a biologist who’d had considerable success giving micronutrients to distressed farm animals. They put together a micronutrient formula of some 36 amino acids, vitamins and minerals – in doses much larger than those available in over-the-counter supplements – and set up a company with the toe-curling name of Truehope.

Some said snake oil, others said miracle cure. Rucklidge, then a PhD student at the University of Calgary, was sceptical.

As a scientist, “it is not a company you necessarily want to affiliate yourself with”, she says. “And I’d been taught diet and nutrition had no place in the treatment of [mental illness]. But as scientists, is it not our role to explore these things?”

Unusually for such companies, the manufacturers wanted scientists to study the formula. And unusually for pharmaceutical developers, they did not ask to be involved in the design of the research.

The resulting study by Rucklidge’s former supervisor, research psychologist Bonnie Kaplan, which followed adults and children diagnosed with bipolar disorder, found a dramatic decline in symptoms.

After arriving in New Zealand in 2000, Rucklidge trialled these same micronutrients with a group of 80 adults with ADHD – at a time when few adults were medicated for the disorder as many health professionals did not believe it continued past childhood.

For eight weeks, half the group took micronutrients while the other half took a placebo. The results, published last year in the British Journal of Psychiatry, showed those receiving micronutrients had improved more than those on the placebo, both in terms of general well-being and ADHD symptoms.

Tim Webb, a participant in the trial and now a contracts manager in Christchurch, was as surprised as anyone. When he was a child, his ADHD made school difficult, he says. “I was always hyperactive. I didn’t seem to be able stay on task, thoughts raced around my head without any real control and I was very impulsive. After 15 minutes in class it was near impossible to concentrate, so you either look like an idiot or you do something silly and you are the class clown.”

After he moved into adulthood, “it never really went away – I just never got the cues”. That led to anxiety, depression and low self-esteem. Anti-depressants didn’t work, and though a course of Ritalin did reduce his symptoms, “it had side effects and it has a street value – it’s not a drug I want to be putting into my body”.

Like others in his situation, Webb self-medicated. “But marijuana’s not good for your memory and it doesn’t do anything about [anxiety], but it would make me seem calm, which was useful.”

After two months on micronutrients, he began to notice the changes. Now, five years later, his memory has improved, he has a full-time job, he’s calmer and he looks after himself better. “You could call it a positive spiral rather than a negative one.”

Still taking the micronutrients? “Religiously. My wife wouldn’t have it any other way.”

Since then, through the University of Canterbury’s newly formed Mental Health and Nutrition Research Group, Rucklidge and her team have been studying the efficacy of two high-dose multinutrient formulae, sold under the brand names NutraTek and Truehope, and probiotics in the treatment of anxiety, insomnia, depression and, in reaction to the Canterbury earthquakes, post-traumatic stress disorder. (Rucklidge is quick to point out neither she nor the university sell or make money from the two main brands.)

Overall, she says, 60-80% of people in these trials respond to micronutrient treatment. These findings come on top of a growing body of international research showing the benefits of broad-spectrum micronutrients in reducing aggression in prisoners, slowing cognitive decline in the elderly, helping people overcome addiction and reducing the symptoms of bipolar disorder, stress, autism and even some cases of psychosis.

TimWebb

Antipsychotic prescriptions double

After each of her published studies, each media report and even, last year, a TEDx talk, the phone calls, emails and letters poured in.

At first she was mystified. “Why were they calling? I knew all the theories, the serotonin hypothesis, the changes in dopamine levels – I thought we’d sorted this. There’s good medication out there. We don’t need to look outside what we are doing because what we are doing is good.”

But what we seem to be doing is identifying more and more people in need of the “good medication”.

Between 1996 and 2014, prescriptions for Pharmac-funded antipsychotics doubled from 200,000 to 400,000. Over the same period, antidepressant prescriptions jumped from just under 400,000 to over a million, even though the difference between the effect of a drug and that of a placebo for mild to moderate depression is as low as 10% (for severe or chronic mental illnesses, this difference leaps to a far more persuasive 70%).

Are we getting better at identifying depression? Are we getting more distressed?

In 2011, international journal BMC Medicine reported that 15% of people in high-income countries suffered from depression at some point in their life, compared with 11% of people in low to middle income countries. Out of 18 countries, New Zealand ranked in the top 25% in nearly every measure of depression.

Professor Malcolm Hopwood at the University of Melbourne, president of the Royal Australian and New Zealand College of Psychiatrists, says with the development of new antidepressant medications with fewer side effects, GPs feel “more comfortable initiating treatments of depression with antidepressant medication”.

And drug treatments, when off-patent, are cheap – certainly cheaper than high-dose micronuturients. In the three years to 2014, the cost to Pharmac of antidepressants fell $8 million to $16.8 million.

Or are we simply pathologising sadness?

Mulder: “Some would argue that all we have done is expand medication to those much less severe and less chronic cases [where] the specific effect is less and the placebo response is more. For mild depression, on balance the benefits may not outweigh the risks. We have to some extent medicalised normal sadness and distress. It is a great capitalist model, frankly. It promotes treatment, it promotes selling medication, but scientists would say we have been oversold this model and the evidence says it does not work well.”

Already the National Institute for Clinical Excellence in the UK has recommended that antidepressants not be used for the initial treatment of mild depression “because the risk-benefit ratio is poor”.

Hopwood agrees that for mild depression, the evidence is quite strong that some forms of psychotherapy – exercise, better work-life balance, dealing with relationship issues – are just as effective as medication.

But responsibility for the growing use of antidepressants should not lie entirely with big pharma or overly eager GPs. He says pressure for prescriptions may come from the patient as much as the doctor.

“Antidepressants are still an effective treatment for moderate to severe depression in particular,” he says. “Many mental health disorders are associated with a risk of relapse, and with depression that risk can perpetuate for a significant period of time. There’s a body of evidence with antidepressants that continuation of treatment dose reduce risk of relapse.”

But the difference between relapse and withdrawal symptoms is not always clear. “Some people say they should stay on [medication] to prevent further episodes,” says Mulder, “but there is not a lot of evidence that is required.”

“Should I come off?”

There is no doubt the psycho-pharmaceutical wave that broke on to the beach of Western medicine in the 1950s helped clear mental health wards. And medication has proved vital in treating acute phases of mental illness and certain chronic conditions.

Where there are genetic factors – as in a small proportion of people with schizophrenia, where people suffer recurrent episodes of depression and have a strong family history, early onset and no obvious precipitants – it’s probably not a bad thing to treat this distress like an illness and manage patients that way, says Mulder. And neither he nor Rucklidge recommend that people stop their medication – such a process, if undertaken at all, needs to be done slowly and under professional care so as to be closely monitored.

But the number of those needing long-term treatment may not be as large as we think, says Mulder, “and we are very poor at predicting who they are”.

Although short-term medication is often effective in dealing with acute symptoms at the early stages of mental illness, it is legitimate to ask a health professional if a change to a lower dose, or no medication at all, is an option further down the track, he says.

“It is a reasonable discussion to have with your mental health professional or GP. To say, ‘I’ve been on this for years, can I come off? Should I come off? What should I do?’

“People could argue that if you have had three severe episodes of depression and you felt suicidal and medication has helped, you might decide to stay on them and that is perfectly legitimate. But if you had one relatively minor episode and have side effects and feel flat, then it’s completely reasonable to think, ‘Why would I want to stay on this?’ It is time to be open-minded about the fact that some people at least might be just as well off medication, or trying other strategies, because the specific effects of medication are less than we have believed.”

He is not saying we should stop taking drugs and that there are no biological contributions to mental illness. “There clearly are, but health professionals have to be more open and say we are not sure what works.

“Most mentally unwell people are competent to make their own decision about treatment and they should be given all this information, rather than just being told this drug will fix you. They certainly shouldn’t be told that if you don’t take your medication, then you can’t be seen by mental health services, which has been said to patients. They should be given the evidence and continue to be monitored, because we know monitoring people and caring for them and giving them hope is a big part of what helps.”

Long-term effects unknown

Missing from this conversation is the availability of long-term research. Many medications are approved on the basis of six-week trials; Rucklidge says there is no requirement, no incentive even, to look at how those drugs are doing in the long term, even though people are put on these drugs for a long time.

“There are people who do well on medications in the short term and the long term, but we also know there is a large number of people who are not well on the medication or who could do better and they are tolerating a lot of side effects. We don’t know how big that group is, but theirs is the voice we need to speak out for.”

Hopwood says regulatory authorities in Australia and New Zealand will require some long-term data for some new medications. A new antidepressant or antipsychotic will be required to show efficacy and safety not just over 6-8 weeks but for up to 12 months, he says. “One could argue 12 months is still a relatively short-term frame. Ideally we would like to look at outcomes over five, 10, 20 years or a lifetime, but those studies are pragmatically difficult and very expensive.”

In the meantime, however, interest is growing in non-medical approaches to mental illness – ongoing therapeutic relationships (including simply participating in a trial), long-term monitoring, diet, exercise. All these factors seem to be important, says Mulder. “All help mobilise that sense of meaning and hope.”

He points to research from the 1960s and 70s showing people with mental illness in developing countries appearing to have better outcomes than those in developed countries. The research, originally undertaken by the World Health Organization, has come under criticism, mainly due to the high attrition rates of participants, but as Mulder says, those diagnosed with schizophrenia in poorer countries seem to do better or at least no worse than those in wealthier countries – “and they would be worse off if they had TB or a broken leg”.

The exact reason is not known. Some say it’s down to alternative treatments such as yoga and meditation, others point to stronger family connections and more opportunities for meaningful work. Mulder suggests, given the lack of access to drug treatments, that those societies may have more tolerance for some symptoms.

“[Those diagnosed with a mental illness] might be more unwell, but they might also be more likely to work and have meaningful relationships. If you are on medication but oversedated, you might not suffer from hallucinations but you’re less able to work or have relationships.

“You might argue that having a few hallucinations – so long as it doesn’t lead to danger to yourself or others – and being able to function is a reasonable compromise. That is an argument we haven’t really engaged in.”

BrainReceptors

Food for thought

An argument that is gathering traction is the importance of micronutrients in mental health. Last month’s annual meeting of the American Psychiatric Association in Toronto included a three-hour symposium on micronutrients as a primary treatment for psychiatric symptoms. In an article in the Lancet Psychiatry journal earlier this year, co-written by Rucklidge, the authors concluded that nutritional medicine “should now be considered as a mainstream element of psychiatric practice, with research, education, policy and health promotion supporting the new framework.”

Already high-quality fish oil has been found to contribute to neurogenesis (creating new brain cells), anti-inflammatory processes and positive modulation of neurotransmitters such as noradrenaline, serotonin and dopamine. S-adenosyl methionine (SAMe), a sulphur-containing compound, has been found to help to regulate mood. There is evidence of the efficacy of the amino acid N-acetylcysteine (NAC) in bipolar depression, schizophrenia and compulsive and addictive behaviours.

Exactly how the vitamins, minerals and amino acids in the formulae Rucklidge and her team are studying affect the brain is not well understood. “But,” says Rucklidge, “all these studies are showing the same thing: nutrients are essential for your mental health.”

A better diet generally can also improve mental health. A Mediterranean-type diet – rich in fruit, vegetables, seafood, olive oil, nuts and legumes – has been shown to lower the risk of mood disorders such as depression and anxiety. In comparison, the higher-calorie, more processed Western diet typically does not meet the recommended intake of several brain-essential nutrients, most notably the B-group vitamins, vitamin D3, zinc, magnesium and omega-3 fatty acids.

Not a single study shows this diet to be good for our mental health, says Rucklidge. And when combined with genetic vulnerability, compromised metabolism, an unhealthy gut, an unhealthy lifestyle and stress – after the Christchurch earthquakes people were found to eat more junk food – such a diet can have a negative effect on mental health.

“So why do we keep eating this way? And why do we think it is okay for our kids to eat this way?” She quotes US science journalist and academic Michael Pollan: if you must shop in a supermarket, shop at the periphery and avoid the processed foods in the centre aisles.

At 28 years of age Kim Newton lost her job. Her health quickly went into decline. She struggled with depression, exhaustion, insomnia, muddled thoughts and lack of appetite. After trying five different antidepressants to no effect, she began researching the role of nutrition and micronutrients, including those studied by Rucklidge and her team. “I was sceptical, but the more reading I did on the subject, the more sure I was.”

She began taking the nutrients, an average of 15 capsules a day, and noticed a “slow, subtle change in my health”. Even now, 11 years later, she says her health is still improving. She has changed her diet to organics and wholefoods, she is exercising, her sleep has improved and last year she completed six of a planned eight papers at the Auckland University of Technology with a B+ average.

“I’m 51 now, but I feel I’m getting younger. When you feel better, you feel more confident, your self-esteem goes up, you can communicate with people and have relationships. If you are lying on your bed in a trance, there is nothing happening in your life.”

Such treatments do not mask symptoms. On micronutrients, children diagnosed with ADHD still display some hyperactivity and impulsivity, says Rucklidge, “but they are calmer, their sleep gets better, they can eat [Ritalin reduces appetite], they are less anxious and they get on better with their peers”.

Unlike those on mood stabilisers such as antidepressants, who often describe a numbing affect, people taking micronutrients “still experience anxiety, sadness, joy. But these are normal emotions that you want to have. We’ve been led to think if a treatment is working, then those symptoms are gone – who cares about quality of life? I am beginning to question our focus on only symptom elimination.”

Which to use first?

Hopwood agrees that treatments for mental health disorders such as schizophrenia and bipolar disorder are not effective for everyone, “and they do come with a relatively high side effect burden, so there is room for additional treatments”.

And he recognises the importance of nutrition, not only in the possible causation of mental health disorders but also in terms of poor nutritional health as a consequence of mental disorder – people with major mental health problems are more at risk of diabetes, respiratory diseases and cardiovascular disease, usually as a result of preventable risk factors such as smoking, physical inactivity, obesity and the side effects of psychiatric medication.

But poorly regulated nutritional advice given to patients has contributed to some reluctance among psychiatrists, he says. “We don’t have sufficient evidence to recommend this as first-line solo treatment for major mental health disorders. And we are not going to support a position saying, ‘This is fine, this is all you need.’ We do have other treatments that have a higher body of evidence that we would still recommend as first line.”

More evidence – more studies, more trials, more long-term monitoring – is clearly needed.

Whereas trials of micronutrient formulae show good results for stress, depression and ADHD, studies on schizophrenia and autism are incomplete. At the University of Canterbury, Rucklidge’s team is running clinical trials on micronutrients in the treatment of ADHD in children, premenstrual syndrome and quit-smoking programmes.

Mulder says it is perfectly reasonable to evaluate micronutrients – or fish oil or exercise or meditation – like any drug undergoing a randomised controlled trial. “One advantage of these things is they have fewer side effects, so if they work just as well, you could argue they should be the first thing we try. If the treatment fails, then we go on to more conventional drugs.”

Rucklidge says medication definitely has a role to play. Psychotherapy, such as cognitive behavioural therapy and mindfulness, still has a place. “But if someone goes to their GP and they are stressed, should the first port of call be an antidepressant? Is it possible that nutrients or nutrition could be explored? We are not there yet, but wouldn’t that be a nice day when we can have that conversation?”

The power of fermented foods; the problem of drugs for mental illness.

BrainVege

‘Micronutrients do seem to work …’

The most common explanation for psychiatric illness is a chemical imbalance or impaired neural circuitry.

The brain relies on a broad range of nutrients for the manufacture of neurotransmitters such as serotonin, dopamine and adrenaline. But no single nutrient has been found to correct such imbalances. Rather, a deficiency in one nutrient is thought to interfere with the absorption and/or metabolism of other nutrients.

The University of Canterbury’s Mental Health and Nutrition Research Group has been studying the efficacy of high-dose multinutrient formulae, including vitamins A, C, D, E and all the Bs, thiamin, riboflavin, magnesium, calcium, iron, phosphorus, iodine, zinc, selenium, copper, manganese, chromium, molybdenum, potassium and some amino acids. Although the results show improvements in a range of psychiatric conditions, the mechanism for these results is not clear.

“It might be [the micronutrients] are assisting the mitochondria, the powerhouses of the cell, to work more effectively,” says University of Canterbury professor of clinical psychology Julia Rucklidge. “Or we are giving the body nutrients to help reduce inflammation or oxidative stress. Or we are just providing the body with what it needs in order for it to function effectively. Micronutrients do seem to work on so many different levels.”

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