Professor Mark Taylor is a consultant psychiatrist at the NHS in the UK. He is also Associate Professor at the University of Queensland in Brisbane Australia.
He is the coauthor of a paper published in the Journal of Psychopharmacology: “First do no harm.” A systematic review of the prevalence and management of antipsychotic adverse effects”.
In this interview we discuss some of his findings and general advice on the detection and management of antipsychotics adverse effects.
We talk about the following topics:
- Why we must pay attention to treatment nonadherence
- What adverse effects have the greatest impact on schizophrenia management
- What are the antipsychotics with the highest risk of metabolic side effects
- What proven strategies can we use to treat antipsychotic-induced metabolic effects
- The Glasgow Antipsychotic Side-effect Scale (GASS)
Interview conducted by Flavio Guzman, MD
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What is the relationship between treatment adherence and antipsychotic side effects?
If you look at the work of Wolfgang Fleischhacker and Peter Weiden, et al., you can see that treatment adherence is negatively impacted by adverse effects of any medication, in this case antipsychotics. It’s worth reiterating that , the WHO (World Health Organization) states that adherence is the number 1 problem with chronic disease management. One in two people don’t take their medicines in the way that we’ve prescribed.
Adherence is the number 1 problem in the management of psychosis and schizophrenia.
Can you categorize the treatment adherence problems we see in our everyday practice?
Quantifying the different elements in the sub-adherence or non-adherence is a bit more tricky, as you know.
There are some people who say ” You’re the crazy one, Dr. Taylor. You can stuff your medicine where the sun doesn’t shine.” There are usually quite a low number in my experience
Secondly, there is partial nonadherence (or covert non-adherence). Patients say: “Look, Dr. Taylor seems like a nice guy. I don’t want to tell him his medicines are rubbish.”
The big group is the partial adherence, the ones who “don’t know what they don’t know”. They are about 90 percent adherent, they think: “Well, I just had a couple of bottles of beer. I don’t really want to take my tablet in case there’s a problem”, which of course is a common misconception.
According to your research, what adverse affects have the greatest impact on treatment adherence?
This is going to sound awfully stereotyped, but the first one is sexual dysfunction, which is probably under-recognized with antipsychotics as a whole. At least half of all the men that were surveyed in all the studies that we reviewed, have some degree of sexual dysfunction. Particularly, younger men have a big problem with the potential of sexual dysfunction. Certainly, I’ve been using a Viagra-type drug sometimes as a consequence for people who are doing well on treatment but have this problem.
And flipping it around, again, it sounds awfully sexist but some of the female patients get very troubled by the weight gain potential. These are both issues of both genders of course.
What about the pathophysiology of sexual side effects?
Good question. You are distinguishing between libido (which we could conceive as centrally mediated sexual interest) and the more peripheral erectile function or orgasmic potential or failure to reach orgasm. You can’t make too much distinction between these two things.
It seems to be that it is more the peripheral apparatus, i.e., erectile function and to some extent delayed ejaculation or delayed orgasmia or anorgasmia. That seems to be what I’m picking up from what I have seen.
There are multiple variables in the equation: age, comorbidity or co-prescription of other medication. It seems to be more a peripheral rather than a central problem, which is why I mentioned the Viagra or sildenafil-type medications as one way of addressing that.
What other effects are patients and physicians concerned about?
It’s interesting to note that old research showed that the extrapyramidal side effects or movement disorders were rated less severely by the patients than the doctors. The doctors used to get quite worried about EPS or parkisonian side effects more than the patients, although I’m not sure we can generalize it these days.
The other common one of course is sedation, which you can harness to good effect. Sometimes, you just employ a sedative antipsychotic at nighttime because sleep is often the problem.
Sedation becomes a problem in the rural areas where driving is essential. For example, when I was in Australia, taking someone’s driving license away from them was like probably the worst insult you could ever say. If sedation is causing driving issues, that can be a big problem.
Regarding second generation antipsychotics, which are the antipsychotics with the greatest and lowest risk of causing type 2 diabetes, weight gain and dyslipidemia?
My take home our research was that clozapine is the worst for metabolic generally. Olanzapine is the worst for weight gain. There’s a sort of gradient down from those two where towards the bottom you got aripiprazole and the new one, lurasidone.
In my mind at least, there is no clear categorical distinction. There is quite a bit of debate in the UK about how the psychiatric profession was bewitched by commercial interest into believing that the new drugs that came out in the mid to late 90s were categorically different in some way and that appears to be not the case.
Are there any strategies that have been proven effective in the management of metabolic side effects?
Sometimes, you have people for example doing well on olanzapine. I’ve got a few patients at the moment who are doing well on olanzapine but you worry about the metabolic consequences. So there are clearly some lifestyle interventions that are crucial here. For example, I always prescribe a 45- to 60-minute walk a day. I require my patients to go walking every day.
Another related issue is the diet. The diet is difficult here in the UK. The best diet as far as I’ve understood is the so-called Mediterranean diet. Having said that, getting some people with schizophrenia over to a more healthy diet is a big challenge. We have a colleague in Scotland called Robin McCravey who switched people over to a healthy diet for six months. He gave them free vegetables and fruits and what have you for six months to try and change their dietary habits. They did change with dietitian advice during that period of the study. But then at the end of the study when the free food stopped, they just moved back to the fried food or the junk food.
I would plug off Scottish Guidelines, SIGN 131.
What about the pharmacological management? Do you have any suggestions?
What I specifically mentioned is use of metformin. I started using that with clozapine and olanzapine sometimes particularly in younger individuals. Some clinicians (not me) even use metformin prophylactically if they feel that clozapine or olanzapine are a good idea. The dosing is 500 mg or 1 gr of slow-release metformin. Metformin is a very safe medicine. The diabetologists like it, it improves insulin sensitivity. It doesn’t send you into a hypo. It’s a very safe medication. You probably wouldn’t want to take it if you got irritable bowel syndrome. But aside from that, it’s quite an easy to use medication. So I have been using metformin a lot more frequently.
The other thing that I’d pass on to your colleagues which they probably know already is low-dose aripiprazole, 5 mg, possibly 10 mg of going alongside as a side order to the olanzapine and clozapine. Not really for its antipsychotic effect but for its corrective metabolic effect.
Those are a couple of medication strategies that I’ve certainly been using in the last couple of years to go along – don’t get me wrong, to go alongside the lifestyle and dietary interventions because what we see from the diabetes world is that if you combine the lifestyle and the dietary with the medication, that’s when you get the best results.
You are one of the authors of the Glasgow Antipsychotic Side-effect Scale. What can you tell us about it?
When we looked at it, the default scale in the UK was one called LUNSERS, Liverpool University Side Effect Rating Scale, which came out in 1993 which was a long time ago before most of the newer drugs. The LUNSERS didn’t really have many of the metabolic questions that we wondered. It was also quite long, three and a bit pages. So we just thought we could do better than that.
We validated the GASS, the Glasgow Antipsychotic Side-effect Scale. I think it seems to have taken off partly because it’s quite short and partly because the language is quite user friendly. We spent a bit of time converting difficult words like galactorrhea into plain English. And maybe partly because it’s free, you don’t have to pay anyone, you can use it if you like it.
The only thing we copyrighted is the intellectual property, Linda and I. So if you want to use it and distribute it, please feel free to go ahead. Certainly in the UK and to some extent Australia, it seems to be the default scale if you’re going to use a scale for side effects.
Are there any final comments you would like to share?
What I would say is let’s try to be evidence based. Let’s think carefully about what we would like for ourselves and do onto others as we’d have done to ourselves. But let’s pay attention to the latest literature and the latest guidelines, the best guidelines. Clearly, over the last decades, there hasn’t really been a breakthrough in the treatment of schizophrenia which is a little bit sad. I know the industry is retrenched or retracted in some ways from these difficult complex mental illnesses but it’s our duty. These are common problems and it’s our duty to keep working away, helping people to the best of our ability.
I think most psychiatrists are not just interested in medications. I’m particularly interested like many other people, but we went into psychiatry to look at other treatment modalities whether it’s psychological therapies, whether it’s lifestyle interventions or whether it’s family interventions. These are all crucial parts of delivering psychiatric treatment.
I like to emphasize that medications are clearly crucial and important but it’s one piece of the jigsaw.
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