Pharmacopsychiatry
Current Developments in Psychopharmacology for the Treatment of Depression and Schizophrenia
Hans-Jürgen Möller Chairman, Department of Psychiatry, Ludwig-Maximilians-University Munich
Abstract
Knowledge in the field of neuroscience is growing fast, as can be seen in the improved understanding of the complex aetiopathogenesis of psychiatric disorders such as schizophrenia, depression, bipolar disorder, anxiety disorders, etc. Besides basic neuroscience and psychopharmacology, in the field of clinical research in particular, neurogenetics and neuroimaging are the most active and promising fields. This could lead to the tempting vision that our currently available psychopharmacological treatments will soon be replaced by other, more effective and more tailored, psychopharmacological approaches. However, this vision has not been fulfilled so far. The theoretically glamorous concepts going beyond the classic transmitter-based approaches, such as substance P antagonism, corticotropin-releasing factor-receptor antagonism, treatments based on interventions in the glutamatergic system, treatments related to neuroplasticity processes etc., are still far away from being introduced as an enrichment of our traditional therapeutic armamentarium. It seems to be much easier to develop and license compounds that more or less follow the traditional ways than to successfully develop these more futuristic approaches. Even in the field of Alzheimer’s disease treatment, the more theoretically advanced approaches, e.g. interventions targeting amyloid deposits such as immunisation strategies as well as secretase inhibitors, have so far not been able to demonstrate a final proof of concept. There is, therefore, disappointment on the part of clinicians as well as the pharmaceutical industry about the current situation and the perspectives for the near future. It can also be observed that the disappointment and general financial restrictions in some pharmaceutical companies have even led to the closure or reduction of their central nervous system research laboratories. This will not only negatively influence the productivity of the pharmaceutical companies in the psychopharmalogical field and restrict the development of new medication, but will also have an impact on neurobiological research and on psychiatry in general.
Keywords Antidepressants, antipsychotics, depression, psychopharmacology, schizophrenia, second-generation antipsychotics, neuroleptics
Disclosure: Hans-Jürgen Möller is a current/past member of the speaker’s bureau for: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Eisai, GlaxoSmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, sanofi-aventis, Sepracor and Servier. He serves/has served as a consultant or is on the advisory board for: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, Sepracor, Servier and Wyeth. He also receives/has received grant/research support from: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Eisai, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, Novartis, Organon, Pfizer, Sanofi-Aventis, Schering-Plough, Schwabe, Sepracor, Servier and Wyeth. Received: 3 February 2011 Accepted: 3 March 2011 Citation: European Psychiatric Review, 2011;4(1):18–20 Correspondence: Hans-Jürgen Möller, Chairman of the Department of Psychiatry, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany. E:
hans-juergen.moeller@
med.uni-muenchen.de
The Future of Antipsychotics
In the field of schizophrenia treatment, second-generation antipsychotics (SGAs) represent progress in the drug treatment of schizophrenia, especially under the aspect of lower liability regarding extrapyramidal symptoms (EPS) and, to a lesser degree, concerning superior efficacy and a broader spectrum of efficacy. The latter results do not absolutely fulfil the expectations which were primarily associated with the advent of SGAs.1
In addition, there is the problem that at least some of the SGAs induce weight gain to a remarkable degree and that this is associated with metabolic risks.2
Clozapine still seems to be the best representative
of the SGAs under different efficacy aspects, especially regarding the efficacy in refractory patients; however, clozapine is also associated with a high risk of weight gain and a low, but possibly fatal, risk of
agranulocytosis. The blockade of cerebral serotonin 5-HT2A receptors and the preferential blockade of specific subtypes of dopamine receptors were hypothesised to be a relevant pharmaceutical mechanism for a lower risk of inducing extrapyramidal side effects and for the efficacy of SGAs in treating negative and depressive symptoms.3,4
For the clinical 18
profile of individual SGAs, the interaction with some other cerebral
receptors, like 5-HT1A for example, might be of importance. It should be mentioned that the indications for SGAs have been expanded into the field of affective disorders such as bipolar mania, bipolar depression and treatment refractory depression.
Current drug development in the field of schizophrenia treatment continues on the one side with the multireceptor approach, combining especially antagonism of different serotonergic and dopaminergic
receptor-subtypes, with some specific alterations. Besides full D2 antagonists, also the D2 partial agonists, a concept which was primarily realised with aripiprazole, are being tested in this context.5
Asenapine,
a recently licensed multireceptor antipsychotic, has demonstrated some positive findings for negative symptoms, even in people with predominant negative symptoms. It is currently not clear whether some of the other antipsychotics under development will provide the progress that is expected in the field of schizophrenia treatment. For example, bifeprunox, a compound with partial agonist activity at D2, D4 and 5-HT1A
© TOUCH BRIEFINGS 2011
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