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SCHIZOPHRENIA
An essay exploring the efficacy of psychopharmacology and metacognitive
training in the treatment of schizophrenia
Schizophrenia is a severe and chronic psychiatric disorder with a multifactorial aetiology*,
which is characterized by delusions, disorganized thinking, hallucinations and bizarre motor
behaviour (psychotic/positive symptoms) as well as apathy, anhedonia*, asociality* and
affect disturbance (deficit/negative symptoms) (Pazooki, Leibetseder, Renner, Gougleris &
Kapsali 2019, p.31). Additionally, many patients also present with cognitive dysfunctions such
as impaired executive function, attention, learning and memory (Bora, 2016; Schaefer,
Giangrade, Weinberger & Dickinson, 2013; Wong & Van Tol 2003). A wide range of biological
and psychosocial treatment options are currently available to treat the disease including -but
not limited to- pharmacotherapy, electroconvulsive therapy (ECT), cognitive-behavioural
therapy for psychosis (CBTp), cognitive remediation training (CRT), metacognitive training
(MCT), psychoeducation, psychodynamic psychotherapy and neurofeedback (Chanpattana et
al., 1999; Chien, Leung, Yeung & Wong, 2013; Moritz & Woodward, 2007; Pazooki et al.,
2019). The primary aim of the present essay is to briefly describe and critically evaluate the
efficacy of drug therapy and MCT in the treatment of schizophrenia.
Antipsychotics, also known as neuroleptics, represent the first line of intervention for
schizophrenia, and arguably the most effective therapy for the psychotic symptoms of the
disease (Davey 2014, p.271). These drugs are usually divided into first-generation/typical
antipsychotics (FGAs) and second-generation/atypical antipsychotics (SGAs). FGAs such as
Haloperidol and Chlorpromazine are antagonists of dopamine D2 receptors that presumably
diminish psychotic symptoms by blocking excess dopamine transmission in the brain, while
SGAs such as Risperidone* and Olanzapine* selectively target various neuroreceptors
including dopamine, serotonin and norepinephrine, to exert their therapeutic effects
(Miyamoto, Duncan, Marx & Lieberman 2005).
Pharmacotherapy has been associated with numerous benefits. Firstly, schizophrenia
patients treated with antipsychotics have been shown to have a lower long-term mortality
risk compared to those without medication (Tiihonen et al., 2009; Vermeulen et al., 2017).
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Additionally, in their meta-analysis of 65 randomized controlled trials (RCTs) with a total of
6493 participants, Leucht, Tardy, Komossa, Kissling and Davis (2012) reported that relative to
placebo, all antipsychotics were significantly more effective in preventing relapse in patients
with schizophrenia at 12 months. Moreover, drug therapy was also found to be superior to
placebo on reducing rates of hospitalization and improving quality of life. However, it must
be noted that the vast majority of studies to date, which investigated the efficacy of various
drug treatments for schizophrenia, were funded by pharmaceutical companies.
Pharmaceutical industry sponsorship has previously been identified as a moderator of
antipsychotic-placebo effectiveness differences (Leucht et al. 2017).
While both classes of drugs have been demonstrated to be superior to placebo, SGAs have
been associated with a greater effectiveness in diminishing negative symptoms (Tollefson &
Sanger 1997) and preventing relapse (Csernansky, Mahmond & Brenner 2002) compared to
traditional antipsychotics. Based on their meta-analysis of over 130 clinical trials, Davis, Chen
and Glick (2003) concluded that relative to FGAs, some atypical antipsychotics- risperidone
and olanzapine in particular- were slightly more effective in diminishing psychotic symptoms
and moderately more efficacious in reducing cognitive and deficit ones. However, it must be
noted that some studies failed to find evidence for the superiority of the second-generation
antipsychotics over the first-generation ones. In a non-commercially funded, multisite RCT
involving 227 schizophrenia patients, Jones et al. (2006) reported that there was no significant
difference between FGAs and SGAs in terms of objective efficacy and subjective patient
preference over a one-year period. A systematic overview and meta-regression analyses of
52 RCTs conducted by Geddes, Freemantle, Harrison and Beddington (2000) yielded similar
results.
Regardless of class, the efficacy of antipsychotics is limited by the fact that these drugs do
not address the underlying issues that lead to the development of schizophrenia symptoms
and as such they have minimal effect on insight (Davey 2014, p.271). In other words, while
antipsychotics can successfully suppress, they cannot eliminate symptoms altogether, thus
patients often require lifelong medication to manage their symptomatology. However, this
can be problematic, given that the rates of partial and complete non-adherence to
antipsychotics remain very high among schizophrenia patients, owing to poor illness insight,
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forgetfulness, stigma, distrust in therapists, and perhaps most notably due to adverse effects
(Higashi et al., 2013; Sendt, Tracy & Bhattacharyya, 2015).
The efficacy of antipsychotics is greatly reduced by their side effect profiles. Both FGAs and
SGAs have been linked to an increased likelihood of cardiac arrhythmias, sedation, headaches
and orthostatic hypotension* (Muench & Hamer 2010). Additionally, SGAs, particularly
clozapine, olanzapine and quetiapine*, have been linked to metabolic syndrome problems
such as type II diabetes mellitus and obesity (Rummel-Kluge et al. 2010), while traditional
antipsychotics have been associated with movement disorders including tardive dyskinesia
(Davey 2014). However, as Muench and Hamer (2010) pointed out, such extrapyramidal side
effects are much more common with haloperidol, which binds strongly to D2 receptors, than
other FGAs such as chlorpromazine, that bind weakly. Furthermore, neuroleptics-particularly
FGAs and among SGAs Risperidone and Amisulpride*- have also been shown to induce
hyperprolactinaemia*, which can cause sexual dysfunction, infertility, decreased bone
mineral density in patients as well as gynecomastia* in men and menstrual irregularities such
as secondary amenorrhea* in women (Peuskens, Pani, Detraux & De Hert, 2014; Seeman,
2011; Tewksbury & Olander, 2016). Moreover, in extremely rare cases, the use of
antipsychotics has been documented to cause to neuroleptic malignant syndrome (NMS)*, a
serious adverse drug reaction, which if left untreated can lead to seizures, rhabdomyolysis*,
acute renal failure, sepsis and death (Mann, Caroff, Keck & Lazarus 2003).
In addition to low treatment-adherence, treatment resistance also poses a problem to
psychopharmacological interventions, as an estimated 30% of sufferers continue to
experience positive symptoms in spite of being on antipsychotic medications (Kane, 2012;
Numata, Umehara, Ohmori & Hashimoto, 2018). Clozapine has been shown to be superior to
all other antipsychotics in managing treatment-resistant schizophrenia (TRS), with an
estimated 50-60% of TRS patients, who are resistant to other SGAs and FGAs, responding well
to clozapine (Lally & MacCabe 2015). However, as Kane (2012) pointed out, clinicians are
often hesitant to prescribe this drug due to its severe side effects and complicated treatment
regime. Clozapine use has been associated with tachycardia, hypersalivation, hypotension,
weight gain, severe headaches, seizures and in about 1% of users the drug has been shown
to produce agranulocytosis*; a potentially life-threatening hematologic disorder (De Berardis
et al., 2018; Numata et al., 2018). Considering that antipsychotics only have a partial impact
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