Schizophrenia: Antipsychotics are effective but unpopular

All available antipsychotics have an antidopaminergic effect. They differ little in terms of efficacy, but differ in side effects. Certain active ingredients or dosage forms are preferred for specific groups of patients with schizophrenia.

Patients with schizophrenia often suffer from auditory, visual, or tactile hallucinations, as well as delusions, typically delusions of attachment and persecution. These are considered positive symptoms. / © Adobe Stock/zakalinka

Schizophrenia usually begins in young adulthood. Approximately 20 percent of patients experience a persistent psychosis, and the same number experience only a single episode. "These vary greatly, often chronic, courses of the disease," explained Professor Dr. Stefan Leucht, head of the Section for Evidence-Based Medicine in Psychiatry and Psychotherapy at the Technical University of Munich, at the Pharmacon continuing education conference in Merano.

Positive symptoms such as hallucinations (auditory, visual, tactile) and delusions, typically paranoia, are often prominent. "But schizophrenia is not a split personality disorder." Some patients primarily suffer from negative symptoms such as lack of motivation and joy, as well as pronounced cognitive deficits.

"All antipsychotics are dopamine blockers that address positive symptoms well but are not effective against negative symptoms," the psychiatrist demonstrated using a network meta-analysis (DOI: 10.1016/S0140-6736(19)31135-3 ). They do not have a nonspecific sedative effect, but rather specifically target positive symptoms.

Leucht recommended that the patient be involved in the selection of medication. A "Shared Decision Making Assistant" (SMDA) for adults with schizophrenia can be helpful in this regard. This allows antipsychotics to be ranked according to their effectiveness and potential side effects, such as weight gain, anticholinergic side effects, movement disorders, or hyperprolactinemia.

On the question of how different subgroups are treated, Leucht and colleagues published a meta-analysis in the journal "The Lancet Psychiatry" in 2022 (DOI: 10.1016/S2215-0366(22)00304-2 ). According to this meta-analysis, a treatment strongly guided by side effects is preferred for children and adolescents, and a lower dosage is preferred for older people to limit side effects.

Professor Dr. Stefan Leucht / © PZ/Alois Müller

First-time patients generally respond very well to antipsychotics. "The more relapses they experience, the worse the response rate," explained the psychiatrist. If patients primarily suffer from negative symptoms, only cariprazine ( _D3 partial agonist) or low-dose amisulpride (15 to 300 mg/day) are "truly effective," the psychiatrist explained. In cases of treatment resistance, clozapine is the drug of choice. For patients with substance abuse, second-generation antipsychotics and depot formulations are preferred. Other drug classes should not be used, except for antidepressants in cases of persistent negative symptoms or depression.

How long does it take for an effect to become noticeable? The theory of the delayed onset of antipsychotics is outdated, Leucht explained. Psychotic symptoms appear as early as the first week, with improvement occurring by week 4. "The greatest effect occurs at the beginning. If nothing happens in the first two weeks, or the patient worsens, it is unlikely that an effect will occur. Therefore, therapy should be adjusted after two to four weeks." However, it can take weeks or months for the full antipsychotic effect to occur.