bipolar: a new entrance to an old rabbit hole

They yap on about how markets and economies are bipolar all the damn time, but of course, there is a real live and dinkum bipolar market – and there will be as long as there’s cash involved. You may have read theories that bipolar disorder is the most expensive medical disorder to treat. I don’t know whether that’s true or not, but it wouldn’t surprise me. And in terms of what we call big pharma and they call the pharmaceuticals industry, this:

Global Bipolar Disorder Market (2015-2020): “U.S. represents the largest market followed by Canada.” The runners up are all European countries and the emerging region is Asia. It’s a market research report about a full report, which you’d have to buy. The press release is brief, interesting to scan and I felt that this was the part you and I would find most fascinating:

However, stringent regulations and side-effects of anticonvulsants hamper the growth of global bipolar disorder market. Moreover, less number of approved anticonvulsants for the treatment of bipolar disorder also obstructs the growth of the market. Increasing mergers and acquisitions between drug manufacturing companies is key trend of the global bipolar disorder market.

Breaks your heart, doesn’t it? How are they going to be able to afford Lear jets???! You guys know me well enough to know that I’m not about to launch into an anti-meds rant, because I am very much pro-psychiatry. I don’t even engage in the anti big pharma thing, it’s pointless; we all know the score there and there’s no protest big enough to change it. I’m interested in how things affect me and that means the treatment itself. Global trends, therefore, are built with the nuts and bolts of dealing with bipolar, and that’s our reality.

Interestingly, owing to the expiration of the patent on Seroquel, the 2015 expiration of the paten on Abilify and declining sales of Zyprexa, by 2019, big pharma is set to lose (wait for it) 65 billions of your American dollars. Bye bye Lear jets? Nope. Forbes says there’s help on the way, in the form of a “boom in brain meds”. There’s a handy breakdown of big pharma stocks there too, in case you’d like to hand them some more money. And besides, according to the World Health Organisation:

The global pharmaceuticals market is worth US$300 billion a year, a figure expected to rise to US$400 billion within three years. The 10 largest drugs companies control over one-third of this market, several with sales of more than US$10 billion a year and profit margins of about 30%.

The crux of that particular matter will not surprise you one bit.

As a result of this pressure to maintain sales, there is now, in WHO’s words, “an inherent conflict of interest between the legitimate business goals of manufacturers and the social, medical and economic needs of providers and the public to select and use drugs in the most rational way”.

Ethics? What ethics?

It’s interesting to read about neuroscience from an economics point of view, rather than an academic one. The information and forecasts are actually presented in a far less arcane way. The payoff is a glimpse at not only how treatment and its meds are liable to progress, but also how the research works, that creates options in the first place.

THE HISTORY OF BRAIN DRUGS IS BASED ALMOST entirely on luck. The first antipsychotic, Thorazine, was tried on schizophrenics in the 1950s as a sedative and miraculously stopped their hallucinations. The first antidepressant, imipramine, was an attempt at making a new antipsychotic that failed but turned out to improve mood

That’s pretty normal, I think? After all, wellbutrin has the surprise side effect of making cigarettes taste like shit and voila – zyban. Anyway, that’s past, what about current research?

Some of the improvements are incremental. Psychiatry clinical trials often fail because placebo groups do better than they should. Part of the problem is that patients can exaggerate their symptoms to get into a study, and developing a relationship with their new doctor actually makes their symptoms seem better.

And the future? Well judging by this, it looks like more genetics and fewer drugs.

In the future, hopes Ricardo Dolmetsch, who heads neuroscience drug discovery at Novartis, when you go to a psychiatrist she’ll consider not only your symptoms but she’ll sequence your genome.
That will allow her to decide on the right combination of two or three drugs to treat what is actually wrong with you. (Thomas Insel, the director of the National Institute of Mental Health, has even proposed creating a new, more genetics-based classification system for mental illness that could eventually replace the weighty bible of conditions that psychiatrists use to diagnose patients and bill insurers.)

(source of previous three quotes – Forbes article)

Bye bye DSM? If you read the article, don’t miss the section at the end, which tells you the direction and outlook of various disorders and their treatment. The next logical step down this particular rabbit hole, is to find some analysis of the economics analysis. You just can’t trust anyone living in a rabbit hole; question everything, kids. Anthropology is my go to faculty for that sort of thing, for obvious reasons. Joseph Dumit was a digression, bit a fabulous one.

Drugs for life – Laurie Taylor talks to the US anthropologist, Joseph Dumit, about his research into the burgeoning consumption of medicine in the US. Dumit did ethnographic research with drug company executives, marketers, researchers, doctors and patients, and assessed the industry’s strategies for expanding their markets. He asks if the huge growth in medication ties us to a radically new conception of ourselves as intrinsically ill and need of treatment. Is this a uniquely American development or does it equally apply to the UK and beyond? He’s joined by the British sociologist, John Abraham. (audio)

tl;dr – yes.

Conclusion? As we’ve already seen, all of that genetic research really could work out and improve things. Market forces, however, will always have the last say. No surprise there. With that in mind, we can peer into the cloudy crystal ball of the future.

Out of the examples shown in 2015, here are two treatment projections that are relevant to us as bipolar sufferers.

DEPRESSION Outlook: Very good. Fast-acting drugs are already in late-stage trials after showing great promise. Currently: Existing drugs take weeks to have an effect. What’s next: Faster-acting drugs. Alkermes is testing one that is in late-stage trials that works in days, not weeks. A J&J inhaled derivative of ketamine and new drugs being developed by Naurex all seem to work in minutes on depression that doesn’t respond to other drugs. Long term: Eli Lilly has a new antidepressant pill that has shown some promise. Johnson & Johnson JNJ -0.3% and Lundbeck are studying how depression might be the result of misfires by the immune system that damage the brain.

SCHIZOPHRENIA Outlook: Fair. Interesting drugs in development but not enough of them. Currently: Drugs can be effective at treating hallucinations and paranoia but don’t yet treat cognitive problems and social difficulties caused by the disease. What’s next: Add-on drugs. In 2016 Forum Pharmaceuticals hopes to have results on its encenicline, aimed at helping schizophrenics think more clearly. Acadia Pharmaceuticals is testing its Nuplazid to help existing antipsychotics. Long term: Intra-Cellular Therapies, a new publicly traded company, is testing a pill that, instead of working outside neurons, gets deep inside them. “It could be the most promising advance in antipsychotic pharmacology [in decades],” says Jeffrey Lieberman, psychiatrist in chief at NewYork-Presbyterian Hospital-Columbia University Medical Center.

(source: the Forbes articles again)

However, there are three research papers from 2013, looking specifically at bipolar disorder, which are certainly still relevant. On the interminable subject of research, the following:

Paper One: “The association between genotype and phenotype for psychiatric disorders is clearly complex,” wrote Professor Nick Craddock, one of the paper’s authors. “The key point is that most cases of bipolar disorder involve the interplay of several genes or more complex genetic mechanisms, together with the effects of the environment, and chance.”
The authors emphasized that bipolar disorder research now needs to follow up genetic studies with imaging and psychological studies in order to try and unravel the complex biological mechanisms involved in bipolar disorder, and bring biological understanding closer to the experience of the patient.

Paper Two: innovative combinations of neuroimaging and pattern recognition approaches might better identify individual patterns of neural structure and function that accurately diagnose a patient’s precise affective disorder.

There’s neuro-news about research all the time, but what’s the way forward?

Paper Three: Combining psychosocial treatments – which can include not just psychotherapy for the patient, but family therapy involving education for their family or caregiver – with mood stabilising drugs might well be one of the most promising lines of treatment for bipolar disorder,” said Professor John Geddes.

2014 yielded the following advances:

Stimulants for bipolar disorder.There is continued debate over the use of stimulants for depression, especially bipolar depression. Research suggests that some stimulants–particularly modafinil and related drugs–can have augmentative effects to standard treatment for bipolar disorder, including possible reduction in manic behaviors.
Functional remediation. Although many interventions have been proven effective in the treatment of bipolar disorder, only a few studies have addressed the issue of functional recovery. A Spanish group reports on a functional remediation program for bipolar disorder, including training in neurocognitive skills for patients to incorporate into their daily routines. This “neuro-cognitive-behavioral” approach shows promise in improving functioning for some groups of patients.

Basically we’re looking at better and tighter diagnoses via genetics, neuroimaging, pattern recognition and psychology. There’s also a relatively new stem cell model which could assist the process. In terms of treatment, there’s development of faster acting antidepressants and better antipsychotics. There’s the possibility of stimulants being used to treat mania and in neurocognitive skills development to help us function better in general. They’ve been researching magnetic stimulation since 2001 too. Lots of balls in the air then.

It struck me that the only method of those mentioned that we might have any access to is neurocognitive training; the rest hinges on the research and the funding behind it. Apparently only a small amount of cognitive impairment is caused by meds. This is how neurocognitive development of the ability to manipulate information in working memory occurs in childhood, adolescence and young adulthood. It’s a good primer. What we need, apparently, is cognitive remediation therapy. After banging my head repeatedly against academia, I resorted (reluctantly) to the collective unconscious of Wikipedia for an explanation fit for the layman:

Narrowly defined, CRT is a set of cognitive drills or compensatory interventions designed to enhance cognitive functioning. However, from the vantage point of the rehabilitation field, CRT engages the participant in a learning activity to enhance the neurocognitive skills relevant to overall recovery goals. CR programs vary in the extent to which they reflect these narrow or broader perspectives, and there is ongoing research to identify the active ingredients that result in a positive response to treatment. Data suggests that when cognitive remediation is provided to people with schizophrenia, it is most effective when given in the broader context of psychosocial rehabilitation. Recent attention has turned to incorporating motivational enhancements into the treatment of cognitive dysfunction for psychological disorders.

So can we do any of it at home? Are those brain training apps and games any good? tl;dr – I’m fucked if I know.

There’s a TBI home-based cognitive stimulation program that gives exercises for a carer do do with the patient/student, at low levels of functioning; if you’re interested to see how it works, grab the pdf here. It’s easy to find stuff for you and a carer to do, after some questionnaires (done with the carer) and the handing over of some dosh, but how about the rest of us? There are more resources for TBI or dementia sufferers than anyone else, which makes sense. There are many research papers dissecting its efficacy and many mentions of computer assisted cognitive remediation for those with schizophrenia. The modules of this computer program, which is used by the patient and facilitated by the medical professional, will give you an idea of the types of activities involved for people like us. There’s a useful study called Personalized Cognitive Training in Unipolar and Bipolar Disorder: A Study of Cognitive Functioning, which isn’t encouraging about the DIY method.

It is unclear which types of cognitive training programs are the most effective in improving cognitive skills (Thompson and Foth, 2005). It appears that training approaches that are designed to accommodate each individual’s neurocognitive strengths and weaknesses, as well as those that offer instant item-specific feedback and dynamically adapt the training program accordingly, are especially effective, particularly in populations with particular cognitive enhancement needs (Whitmer and Gotlib, 2012).

There’s a metric fucktonne of train your brain info out there, but I didn’t come across any that handled anything other than “normal” memory loss and so on. None of it referenced, for example, the inability to form mental connections as a contributing factor. Also, you already know the benefits of reading, sleeping, exercising and eating right, right? Right.

My google fu has google failed to find anything helpful, but I’ve learned a whole bunch and hopefully exercised my brain a little in the process. And hopefully some of you will know stuff too.

Click this for summaries of the latest research into bipolar disorder.

*raises hand* I have a question, HOW ARE YOU GOING TO MAKE THE FUCKING MIXED EPISODES GO AWAY? *cough*