EPA 2020 – Managing acute exacerbations of schizophrenia needs a treatment that will not only work in the short-term, but also take into consideration the long-term needs of patients, according to Prof. José Manuel Montes, Head of Psychiatry at the Hospital Universitario Ramón y Cajal in Madrid. He discussed the clinical experience of using cariprazine in patients with acute schizophrenia during an expert lecture at the virtual 28th European Congress of Psychiatry. Specifically, Prof. Montes overviewed the clinical efficacy and safety and tolerability profile of cariprazine and gave a practical insight on how it might be used in everyday practice.

The goal of schizophrenia treatment in the acute setting is to get the patient back to functioning as normally as possible as quickly as possible, Prof. Montes said. That means not only addressing the immediate needs and controlling patients’ symptoms but also thinking about the long-term benefits and possible side effects of interventions.

Schizophrenia consists of many well-described domains that can affect how a person functions in society and at work. Over the years, treatment has evolved from just focussing on the positive symptoms of schizophrenia (hallucinations, delusions, and disorganized speech and behaviour) to also addressing the negative symptoms (flat affect, social and emotional withdrawal), the cognitive symptoms (attention and memory problems, impaired executive function and decision making), and affective symptoms (dysphoria, anxiety and depression).

All of these symptoms are important to consider when treating schizophrenia and should be born in mind even when treating someone in the acute setting, Prof. Montes said, re-emphasizing the ultimate goal of getting the patient back to as normal a life as possible.

Effectively controlling symptoms ideally while avoiding or causing minimal side-effects, both in the short- and long-term is key as both can influence adherence to treatment, Prof. Montes said. He commented that there was a need to consider that patients might tolerate a treatment and its side effects while hospitalised for an acute exacerbation, but that once discharged they may not be as adherent and perhaps discontinue their medication.

Adherence is a complex issue, Prof. Montes acknowledged, but it is important to try to achieve as it is linked to the risk of relapse. Data have shown that patients’ attitudes towards treatment in the future is related to their first admission experience and having a bad experience in the hospital could have an effect on patients’ future levels of adherence.¹ Thus selecting treatment in the acute schizophrenia setting needs to be a collaborative effort and not coercing patients into receiving treatments that they will not tolerate. A very good relationship with patients and their families is needed in order to improve their care, Prof Montes said.

Choosing antipsychotic therapy for an acute episode of schizophrenia needs to factor in symptom control, side effects and patients’ previous experiences and treatment choice, Prof. Montes said. Tolerability is a big issue and this has shown to be different among the various antipsychotic agents. For instance while the first-generation antipsychotics are likely to cause side effects such as extrapyramidal symptoms and sedation, among many other effects, the second-generation antipsychotics are more likely to be associated with weight gain and metabolic disturbances, although this of course varies according to the type of second-generation antipsychotic used.²

The effects of antipsychotics may be influenced by the way they block important receptors associated with the pathophysiology of schizophrenia, Prof. Montes, observed, and introduced cariprazine as one of the newer atypical antipsychotics^3,4 that had a specific receptor binding profile. Cariprazine is a partial agonist of dopamine (D)₃, D₂ and serotonin (5‑HT)_1A receptors and is an antagonist at serotonin 5‑HT_2B receptors.⁴

One of the most important adverse events associated with cariprazine is akathisia, Prof. Montes said. He observed that it occurred at a rate of 12.5% at the highest recommended target dose range (4.5-6 mg/day) of cariprazine in a pooled analysis of four phase II/III randomised, double-blind, placebo-controlled studies. In comparison akathisia had occurred in 3.6% of placebo-treated patients.⁵ Another frequent adverse effect is parkinsonism, reported to occur in 17.5% of patients in clinical trials, although like akathisia, most events were mild to moderate in severity.⁴ Other adverse effects of note were extrapyramidal symptoms, Prof. Montes said, occurring in 18.8% of cariprazine (4.5-6mg/day) and 7.7% of placebo-treated patients in the pooled trials analysis.⁵

But what are the side effects that are of most concern to patients? Prof. Montes highlighted that survey data had indicated that patients with schizophrenia were more concerned about gaining weight, not being able to concentrate, memory loss or having disordered thoughts.⁶ These were (mostly) not side effects that were greatly associated with cariprazine use, Prof. Montes argued andsummarize that cariprazine was an antipsychotic that was well tolerated and thus well suited to being started in the acute setting and continued into the maintenance phase of schizophrenia treatment.^4,5

Turning his focus to the efficacy of cariprazine in controlling the acute symptoms of schizophrenia, Prof. Montes observed that there were data from several short-term trials showing its benefits over placebo on positive symptoms. ^7,8,9 Cariprazine was also effective in reducing hostility, which is particularly important during hospitalisation for an acute exacerbation.¹⁰ Cariprazine had a beneficial effect on negative symptoms of schizophrenia.¹¹

This improvement in all these symptoms, however, must be matched with an improvement in functioning, the ultimate goal of treating patients with schizophrenia, Prof. Montes said. He suggested that pragmatic measures were needed to help improve personal and social relationships, self-care, reduce disturbing and aggressive behaviours, all of which are very important for the long-term care of patients. Study data have shown that cariprazine also has a beneficial effect on patients’ functioning, with statistically significant effects seen in the Personal and Social Performance scale subdomains. ¹¹ This scale reflects activities of daily living such as socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behaviours.

Prof. Montes ended his presentation by discussing some real life-clinical studies to highlight how cariprazine might be used to control acute episodes of schizophrenia. Both were cases of women – one aged 54 years and one aged 36 years – with diagnoses of schizophrenia in the past.

In the case of the older woman, she had experienced psychotic episodes 10 years ago and was treated with the atypical antipsychotic olanzapine. She had developed prominent negative symptoms in the past few years, becoming increasingly withdrawn socially, with low mood and apathy. Her dose of olanzapine had been reduced and started treatment with the antidepressant duloxetine, 60 mg/day. Despite this change in her medication she was not doing well. She was admitted to the emergency department of the hospital after trying to take her own life but she refused to take olanzapine for fear of weight gain and sedation. She is treated with cariprazine 6 mg/day and diazepam 10 mg and gradually her mood lifts and she starts engaging with staff and other patients. Her ideas of death disappear and she accepted her current treatment and is able to be discharged home.

The younger woman had been diagnosed 5 years ago and was being treated with the partial dopamine agonist aripiprazole, 5 mg/day. She had had a stable mental state until recently, during the COVID-19 pandemic, she restarted smoking cannabis to reduce her anxiety. Her dose of aripiprazole was increased to 20 mg/day. She is admitted to hospital for acute psychosis after screaming in a supermarket that she was there to spread the virus. She is hostile during interviews and thinks the world needs a restart. Her current treatment is discontinued and cariprazine is started. She is also treated with quetiapine 50 mg to control insomnia. Her dose of cariprazine was increased to 6 mg and she begins to become calmer and more cooperative and realises that she was having a re-emergence of her illness. After a few days of stability she is able to be discharged home.

Concluding his talk, Prof. Montes said that cariprazine is effective for treating acute schizophrenia, having effects on multiple dimensions of schizophrenia, including positive symptoms, ^7,8,9 hostility,¹⁰ negative symptoms, ¹¹ and patient functioning. ¹¹ It also has a safety and tolerability profile that lends it to being continued into the maintenance setting. ^4,5