Ketamine for negative & depressive symptoms of schizophrenia

Schizophrenia is a mental illness that causes considerable suffering to those affected by the illness and their families. The acute phase of schizophrenia is called psychosis. Typical symptoms include hearing of voices, feelings of persecution, or disordered thinking. These symptoms, also called "positive symptoms", are very characteristic and usually associated with behavioral alterations, so that the illness can be diagnosed quickly and accurately. With timely treatment, positive symptoms often regress completely. "Negative symptoms of schizophrenia," such as lack of energy, loss of interest, poverty of speech and emotional and social withdrawal, are much more difficult to treat. Negative symptoms often make it difficult for patients to cope with everyday life or work. Relatives also experience negative symptoms as a great burden. In addition, patients with negative symptoms often also suffer from depression. In contrast to their effect on positive symptoms, currently available antipsychotic drugs have inadequate and delayed effects on negative symptoms. Here, we investigate whether ketamine could be a rapid acting and well tolerated treatment for negative and depressive symptoms of schizophrenia. Ketamine is used for short anesthesia and in emergency medicine. It has been known for some time to have reliable and rapid antidepressant effects. In the brain, ketamine acts via the neurotransmitter glutamate and triggers sensations of being far away from the body and oneself. Colors, thoughts and emotions are perceived more intensely. This has led to concern that ketamine could lead to psychosis in those with predisposition or history of psychosis. Therefore, ketamine is not currently used if psychotic symptoms are present. Another reason for concern is older literature on phencyclidine, a drug that is similar to ketamine and thought to induce psychotic illness. After intensive screening of the literature on phencyclidine we came to the conclusion this fear has little scientific basis. Moreover, anecdotal reports suggesting that ketamine may be effective for negative and depressive symptoms without exacerbating psychotic symptoms have recently been published. In this project, patients with negative symptoms are randomly assigned to receive ketamine or a placebo. Close monitoring and regular psychiatric examinations will ensure that adverse treatment effects are quickly identified and treated. Repeated magnetic resonance imaging of the brain should also provide initial clues to the mode of action of ketamine on negative symptoms. If this trial confirms our assumptions on the efficacy and tolerability in negative symptoms, would be an important step in the development of reliable and rapidly effective drugs for treating negative symptoms of schizophrenia.