Treatment of Schizophrenia

When the first antipsychotic drugs, also known as classical neuroleptics or first-generation antipsychotics, were introduced into clinical practice in the 1950s it marked the beginning of a genuine revolution in the history of medicine. The first example was chlorpromazine, which was discovered in 1952 by Delay and Deniker. In 1958, Paul Janssen introduced haloperidol, a cornerstone of schizophrenia treatment for three decades.

In the early 1990s, the first second-generation antipsychotics were marketed, including risperidone, olanzapine, quetiapine, amisulpride, ziprasidone and aripiprazole. More recently, lurasidone and cariprazine have also appeared on the market. Clozapine deserves a special mention as the first member of this group of atypical antipsychotics. It was developed and marketed in the 1970s and indicated especially for treating patients with treatment-resistant schizophrenia.

From the patient’s and their family’s point of view, the basic difference lies in the fact that second-generation antipsychotics are universally more effective and less likely to have negative effects on their motor function (rigidity, lack of facial expression or an inability to express oneself through gestures (amimia), restlessness), level of sedation, mood or intellectual capacity. However, a disadvantage of the new antipsychotics is that some of them bring about weight gain and other metabolic problems. In addition, clozapine can cause a decrease in the number of white blood cells that defend against infections, which is why frequent blood tests are required at the beginning of the treatment.

Another important point to consider is that antipsychotics must be taken for at least 2 to 3 weeks before they start to act on certain symptoms, and this period can be extended up to 6 to 8 weeks in the case of clozapine. It is this time delay until the onset of action that often justifies a hospital stay for longer than two weeks.

In order to ensure antipsychotic coverage lasts for several weeks, the classic or conventional antipsychotics were developed into their depot form (fluphenazine, pipotiazine or zuclopenthixol) which, although effective, produced unfavourable side effects (post-administrative sedation, low blood pressure, extrapyramidal symptoms, etc.).

Recently, by means of more complex technology, risperidone, paliperidone, olanzapine and aripiprazole have been introduced as atypical antipsychotics with a long-acting formulation that combine the aforementioned advantages of second-generation antipsychotics with those of long-acting injectable formulations. They only have to be administered every two or four weeks (depends on each medicine) and so family members no longer have to worry about a daily drug regime.

In the last 5 years, we have had 3-monthly administration formulations of paliperidone palmitate. However, very recently, for the first time in the history of psychopharmacology, we have a 6-monthly administration formulation; this makes maintenance treatment with antipsychotics possible with only two injections per year.

It is important to highlight that oral antipsychotics may also be required temporarily while beginning the administration of some of these long-acting drugs.

Finally, it should be stressed that long-acting antipsychotics, although initially more expensive, prevent relapses and reduce the rates of hospitalisation, thus reducing the economic cost associated with schizophrenia.