Treatment of psychotic disorders

1.7.1 Antipsychotic drug treatment

Medical treatment in psychotic disorders aims to reduce symptoms in the acute phase, while maintaining this improvement through the recovery phase. Preventing or reversing functional loss is also central to attaining the best quality of life possible.

Antipsychotic drugs were discovered in the 50s and have since been a mainstay of psychosis treatment according to clinical guidelines (NICE, 2014; Norwegian Directorate of Health, 2013). First-generation antipsychotics had sedative effects as well as dampening positive symptoms like hallucinations and delusions, and were a big improvement to existing treatments, which were mainly based on containment or heavy sedation of the patient. The advent in the late 80s of clozapine (Kane,

Honigfeld, Singer, & Meltzer, 1988) and subsequently a wider range of second-generation or atypical antipsychotic drugs brought more tolerable drugs promising fewer extrapyramidal side effects, which was a problem with First-generation antipsychotic drugs (Leucht et al., 2009). However, extrapyramidal side effects remain an issue (Divac, Prostran, Jakovcevski, & Cerovac, 2014; Rummel-Kluge et al., 2012). Although current Norwegian national guidelines stipulate that patients be offered non-pharmacological interventions if they wish (Norwegian Directorate of Health, 2013), antipsychotics remain the cornerstone of first-line treatment of acute psychosis, as well as for the maintenance phase (APA, 2006; Kreyenbuhl, Buchanan, Dickerson, & Dixon, 2010; NICE, 2014; Sohler et al., 2016). Due to the symptomatic complexity and severity in this patient group, many will also receive other

psychotropic drugs including mood stabilizers, anxiolytics, sedatives, or antidepressants.

Antipsychotic treatment is often continued for several years after an acute episode in order to minimise risk of relapse, and guidelines recommend continuing medication for 1-2 years after a first episode, or up to 5 years after a relapse (NICE, 2014;

Norwegian Directorate of Health, 2013). Still, discontinuation of drugs or poor compliance is common in psychotic disorders: as symptoms improve, disadvantages like weight gain and metabolic syndrome may seem to outweigh benefits (Sendt,

Tracy, & Bhattacharyya, 2015), even though discontinuation increases the risk of relapse. Although some studies also show that dose reduction or cessation of antipsychotics is associated with higher rates of functional recovery (Wunderink, Nieboer, Wiersma, Sytema, & Nienhuis, 2013) it is difficult in general to untangle whether this is due to the drug, or due to the fact that dose reduction in itself is a symptom of a budding recovery process.

Despite existing guidelines, the ideal length of antipsychotic treatment for each individual cannot easily be determined based on current knowledge (Bjornestad et al., 2017). Atypical antipsychotic drugs are quite effective for the treatment of acute positive symptoms, with about 50-80% of recipients experiencing improvement in positive symptom load, as compared to 5-40% of groups receiving placebo treatment (Buchanan et al., 2010; Dixon, Lehman, & Levine, 1995; Leucht et al., 2012).

However, for patients requiring the trial of a second antipsychotic due to non-response, the response rate may fall to below 20% (Agid et al., 2011). Although on a group level, several factors including female gender, drug naivety and shorter DUP appear to predict a better response (Zhu et al., 2017), it is still uncertain on an individual level why certain patients respond well to antipsychotics while others do not. Despite large metastudies indicating that some AA are more effective than others (Leucht et al., 2013), we also do not know how to predict individual responses to individual drugs. The Bergen Psychosis Project 2 aimed amongst other things to investigate factors which might affect individual drug responses.

1.7.2 Psychosocial treatment

Non-pharmacological and psychosocial interventions are an important part of psychosis treatment, and physical exercise, social contact, art and music therapy are recommended by guidelines (Norwegian Directorate of Health, 2013). Talking therapies are important tools in reducing symptom load, but unlike medication they may also build life skills and support the person and their social surroundings to understand and cope with the disorder.

The main recommended psychotherapeutic approach for psychotic disorders is cognitive behavioural therapy (NICE, 2014; Norwegian Directorate of Health, 2013)

Although these recommendations have been criticized (Jauhar et al., 2014), cognitive-behavioural therapy (CBT) has shown consistently positive effects on positive symptoms of schizophrenia spectrum disorders (Zimmermann, Favrod, Trieu, & Pomini, 2005) and may also reduce the risk of developing psychosis in high-risk groups (Hutton & Taylor, 2014). CBT primarily aims to reduce symptom load and distress, but also to improve general functioning. Other approaches include metacognitive narrative therapy, which aims to ameliorate impairments in the ability to organize information about self, others and the world into complex ideas, allowing the person to build intrinsic and personal motivation for recovery (Lysaker &

Dimaggio, 2014). Mindfulness based interventions are a third-wave cognitive therapy which encourage presence in the moment, acceptance, detachment, and compassion in placement of reactivity, struggling and judgement, aiming to alleviate distress arising from stressful attempts at controlling psychotic symptoms (Khoury, Lecomte, Gaudiano, & Paquin, 2013). Psychoeducative family based interventions have been successful in reducing relapse rates through the reduction of expressed emotion (McFarlane, 2016), in addition to building coping skills in both the patient and their next of kin (Onwumere, Bebbington, & Kuipers, 2011). Multiple-family groups have been found superior to single family groups, indicating a positive effect of social interaction between families (McFarlane, 2016). Psychosocial treatments may also improve drug compliance by reducing paranoid though patterns and building therapeutic relations and illness insight (Higashi et al., 2013).

Despite decades of intense efforts, the aetiology and pathogenesis of psychosis remains unclear, which impedes the development of treatment for schizophrenia.

However, new non-medical treatments are continually being developed, partly in response to scientific and technological advancement. Non-invasive transcranial magnetic stimulation may have a moderate effect on negative symptoms (Aleman, Enriquez-Geppert, Knegtering, & Dlabac-de Lange, 2018) and may potentially also ameliorate cognitive impairment, although previously reported effects on auditory hallucinations have been limited (Slotema, Blom, van Lutterveld, Hoek, & Sommer, 2014). Avatar based virtual reality treatment and other digitally delivered

interventions are also an interesting and promising addition to available treatments

(Rus-Calafell & Schneider, 2020). Cognitive remediation interventions have also shown promising results and is described in more detail in section 1.8.7.