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Antipsychotics and the Link Between Metabolic Syndrome and Schizophrenia By Prof Bernhard Baune

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Prof Bernhard Baune, Ph.D., MD, MPH, FRANZCP, holds the Cato Chair and is Head of Psychiatry at the  University of Melbourne. In 2011, he was appointed as Chair of Psychiatry and Head of Discipline of Psychiatry at the University of Adelaide. Under his leadership, psychiatry research at the University of Adelaide gained international recognition for excellence in neuroimmunology and genomics of mental disorders, and for innovation in molecular and clinical underpinnings of personalized psychiatry. Prof Baune has authored or co-authored 204  peer-reviewed publications and 14 book chapters. 

I will show you in the next few slides some data on the resident and before i do this i would like to clarify briefly the pharmacology so it’s a potent d2 and 5-ht 2a antagonist but for cognition is important to note that there is a affinity to 5-ht 7 receptor which has a role in cognition and also in depressive symptoms which we talked about before but also the

Partial agonist ability to modify the 5-htt 1a receptor has relationship to cognition as well and the moderate and i2c antagonism has also a role in cognition and these are receptors which are not just sort of being associated with cognition but also in animal models have shown to be relevant for cognition like behaviors in small animals like mice and rats and in

Humans that has been shown to express in brain areas which are shown to be a key key areas and functional areas of cognition so here are in the next few slides some some data on studies where rosa down was used as well as other medications to look at the effects on cognitive functions now ecology functions are usually measured by you know you know large concepts

Batteries or objective measures of cognitive function for example the tribe making test here the tmt r the memory test concentration test processing speed test and very often in these types of studies we have the individual test results as you can see here but also a composite score which is kind of taking all the individual test results together to arrive at an

Overall cognition score so which is usually you know expressed as a composite score here and what you can very clearly see is that rather down for example in some of the you know overall there’s a nominal nominal improvement on the in the effect size which is shown here or 0.17 which is a small effect size but some of the mesh achieve higher effect sizes here and

Also the computed score has a sort of a smaller x axis now the key question on effect size could be a whole talk in itself so sometimes we say all the facts out of 0.5 or 0.6 0.7 is clinically meaningful however in individual cognitive scores a smaller effect size might have actually larger functional implications in patients or which is really important to note

Then here we have other studies which so show similar results for example rather than here on cognition in the clock state which is a qualitative test battery here again improving in terms of here effect size in the sorry the composites that’s called the change here for resident hundred sixty milligrams and improving that particularly compared here to placebo and

Here for example quetiapine having a negative effect on that and similar results we see also over long term periods over three and six months here so this is three months and is six months extension studies here again for the resident having positive effect and significantly better effects than for quetiapine for example in direct comparison over the long period of

Time and here is an extension even into 32 weeks of the of comparison again on different domains of cognition and as you can see there’s a there’s a good and statistically significant or at least a numerical improvement on all of these cognitive scores so that speaks to the fact that we have you know positive effects on for resident comparison to other antipsychotic

Medication but more importantly the residence receptor profile actually helps to improve these important qualitative domains in addition obviously to the antipsychotic medication now the second part of my talk is around physical health and comorbidities as we’ve mentioned before so metabolic syndrome has gained a lot of attention in that area and metabolic syndrome

Just as a member as a reminder has here there different elements you know of elevated plasma glucose levels of obesity hdl cholesterol levels triglycerides and also hypertension so all of the when they come together obviously they make up the metabolic syndrome and that’s what we’re talking about in the next few slides here in australia in psychosis or the cardio

Metabolic risk factors have shown this type of distribution so the highest eighty one point sorry eighty two point one percent of patients have increased waist certain firenze high-density lipoproteins half of the patients nearly half of the patients also hypertension triglycerides increase and also plasma glucose in around twenty eight percent of patients you

Can see the the relationship between bmi and physical activity so that patients obviously with psychosis have a you know at least a very high nearly in all of these 56 percent have obese conditions and around overweight is another thirty percent so we have nearly eighty percent of patients with obesity or overweight so which is really large and that correlates

Obviously with low activity here or physical activity or very low even so nearly all of patients have a very low activity there’s a very close relationship there now in terms of the effects of antipsychotic medications on these metabolic conditions we have you know gain quite a lot of knowledge for example along these receptors which are relevant for the academy

Robotic actions or h1 + 3 + 5 h2 to see with clozapine olanzapine having a high metabolic risk risperidone pilot heard on could type in a sort of moderate risk depending on the receptor activity here and the low metabolic risk are the president our purpose or rosa damascena theme so this arcanist is really important to that we get a better understanding of what

The risk profile of the medication is we are using for our patients now you can also express it differently in the number knee to harm so how many patients need to be treated basically in order to induce a weight gain in this case of more than seven or more than seven percent so here for example on the right hand side or lanza pin you need to treat one in six

Patients you know will then have waking of seven or more percent and on the left hand side one in sixty-three patients with treatable atutor will have that that type of weight gain so this kind of gives us a really nice risk stratification of medication to use it doesn’t mean necessary that all patients need to be treated with latura and no needs to be treated

With lalanne subpoena that’s not the message the message is that we need to be aware of that risk stratification and then apply that to individual patients to individual patient settings of what is best for the patient at that at a certain point in time and also in the long term but these figures are really important for us for clinical decision making programs

Now in the next few slides i will briefly show you the effects of different antipsychotic medications on aspects and components of the metabolic syndrome starting here with weight and bmi and this is always the same design looking for change at a change from baseline to week six as a follow-up so here we have the the types of medication as you can see here rather

Down olanzapine quetiapine risperidone haloperidol and they’re all compared to placebo so here we see the baseline and and then the the means here for bmi weight you know over time and the mean change which you can see here is expressed here so there’s little effects of these drugs which have a low bar for rosa dern and risperidone haloperidol of weight and bmi and

For land subpoena quetiapine we have high changes in those airs which are very well aware of now whilst bmi important there’s a lot of research now going on on bmi and the effect actually on brain in relation to brain structure in relation to brain function and one of the effects here which is shown in this particular study in a 200 patients which were readmitted

To hospital with kids due to schizophrenia it was shown actually that they the higher bmi levels or the median of 28.5 kilograms per square meter in a body surface were was that cut off basically saying that this was an independent predictor for readmission so it’s a very close relationship there and this is not just a marker like a surrogate marker of something

Else of unhealthy lifestyles or whatever it is probably related to much more negative effect on brain function in itself on brain metabolism maybe also some effects of the medicaid of bmi on reduced efficacy of medications as such so it’s really an important association probably also a causal association here and now looking at cholesterol very similar findings

Triglycerides which are other components of the metabolic syndrome again here we see for for the similar drugs like raza down and have a peridot actually negative effects on cholesterol and triglyceride so this and decrease and the increase we see again similar for cholesterol triglycerides here for letsa people type in and risperidone compared to placebo similar

Picture again for ldl and hdl cholesterol again more positive is it looks for raza down and similar to placebo levels here again olanzapine being being less less positive as well as photography in glucose and hb h1c again really important measures which we should measure really on a more regular basis and here you see a slightly different picture that most of the

Antipsychotic medications evenly haloperidol type ones they would have negative effects on increasing glucose levels here whereas adult has has no effect there and hb h1c consequently has you know has been negative affected also by or lanza peed here as well now insulin levels as you know insulin is a marker of glucose metabolism and long-term increased levels of

Insulin very negative for for for glucose metabolism but also obviously increases the risk for insulin resistance which is a precursor of type 2 diabetes for example so here again so therefore it’s important to look at the resident here negative effects so a decrease on on that between baseline and and follow-up and again impairing effect basically on increasing

Insulin levels here by olanzapine and quota you

Transcribed from video
Antipsychotics and the Link Between Metabolic Syndrome and Schizophrenia By Prof Bernhard Baune By Dr Sanil Rege’s Hub – Psychiatry Simplified