Treatment of Schizophrenia

The currently available treatments for schizophrenia leave much to be desired, and the search for more effective treatments for both the positive psychotic symptoms of schizophrenia (e.g., hallucinations and delusions) as well as cognitive deficits and negative symptoms is a highly active area of research. Despite this lack, treatment methods have improved drastically in recent years.

Schizophrenia was long considered a lifelong illness with little or no hope of recovery. Following the introduction of antipsychotics more than sixty years ago, treatment prospects were initially modest, with clinicians settling for outcomes such as behavioral control, symptom control, or stability. However, advances in pharmacological treatment and psychosocial interventions have heightened expectations for outcomes. Indeed, there has been a progression of treatment goals from containment to remission through response, and more recently, to recovery. Recovery became a focus of attention when it was recognized that symptom reduction alone was not sufficient, and that functionality and outcomes that are most meaningful to patients and families need to be considered. There is growing acknowledgment that people with schizophrenia do not inevitably experience deterioration over time, and most have the potential to experience considerable symptomatic improvement and achieve a substantial degree of recovery.

A South African study of 98 individuals with schizophrenia studied over two years showed that most improvement occurred within the first six months of treatment with antipsychotic medications, and symptom remission was achieved by 70% of patients. Over half of the patients met the criteria for functional remission and good quality of life, though only 29% met the researchers’ full criteria for recovery. Patients who met the recovery criteria had better premorbid adjustment, were less likely to be of mixed ethnicity, and less likely to use substances.^[1]

Emergency room (ER) visits and subsequent hospitalization for schizophrenia is common, especially for first psychotic episodes. An analysis of National Hospital Ambulatory Medical Care Survey data indicates that during 2009–2011, an average of 382,000 ER visits related to schizophrenia occurred each year among adults aged 18–64, corresponding to an overall visit rate of 20.1 per 10,000 adults. This same study concluded that of the ER visits related to schizophrenia, 32% resulted in a hospital admission, which is higher than ER visits not related to schizophrenia (10.3%). An additional 16.7% of ER visits related to schizophrenia resulted in a transfer to a psychiatric hospital. This was higher than the percentage of ER visits not related to schizophrenia (0.7%).^[2]

Voluntary or involuntary admittance to hospitals may be needed to treat a severe psychotic episode; however, hospital stays are as short as possible. In-patient treatment methods aim to manage psychotic symptoms and ensure that needs, such as safety and nutrition needs, are met. Once symptoms are medications are stable, the goal is to help patients live independently, though in some cases, individuals remain in psychiatric care facilities.

Antipsychotic Medications

The first line of treatment for schizophrenia and other psychotic disorders is the use of antipsychotic medications.

Antipsychotic drug treatment is a key component of the schizophrenia treatment recommendations from the National Institute of Health and Care Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The main aim of treatment with antipsychotics is to reduce the positive symptoms of psychosis that include delusions and hallucinations. There is mixed evidence to support a significant impact of antipsychotic use on negative symptoms (such as apathy, lack of emotional affect, and lack of interest in social interactions) or on the cognitive symptoms (memory impairments, confused or illogical speech, and reduced ability to plan and execute tasks). In general, the efficacy of antipsychotic treatment in reducing both positive and negative symptoms appears greater for those with more intense baseline schizophrenia symptoms. Currently, research suggests that there are at least five different types of dopamine receptors (D1 through D5), although they are often categorized as either the D1-like family (D1 and D5) or the D2-like family (D2, D3, and D4). All available antipsychotic medications work relatively the same way: by antagonizing (blocking) D2-dopamine receptors.

There are two primary types of antipsychotic medications, referred to as typical (first-generation) and atypical (second generation). The fact that typical antipsychotics helped reduce positive symptoms of schizophrenia was discovered serendipitously in the 1960s (Carpenter & Davis, 2012; Lopez-Munoz et al., 2005) and contributed to the dopamine hypothesis for the etiology of schizophrenia. In other words, the reasoning was that if excessive levels of dopamine were a primary cause of psychotic symptoms, then drugs that block dopamine binding at receptors should reduce those symptoms. Over time, as research continued, it has become clear that the etiology of psychotic symptoms is much more complex. For example, although some patients diagnosed with schizophrenia for at least a decade were found to have a 90% blockade of D2 receptors, antipsychotics did not appear to significantly reduce psychotic symptoms. Also, although these drugs may drop dopamine levels significantly within minutes, reduction in symptoms may not occur for days. Other studies have shown that atypical antipsychotics seem to reduce psychotic symptoms about as effectively as the typical antipsychotics, but they are weak antagonists for D2 receptors. Currently, many scientists believe that at least three neurotransmitters are involved in schizophrenia spectrum disorders: dopamine, serotonin, and glutamate. We are still trying to understand the interactions of these systems.

The first-generation (typical) antipsychotic medications are drugs that share the common feature of producing a strong blockade of the D2-type dopamine receptor. Although these drugs can help reduce hallucinations, delusions, and disorganized speech, they do little to improve cognitive deficits or negative symptoms and can be associated with distressing motor side effects that can become permanent over time. The newer atypical antipsychotics have more mixed mechanisms of action in terms of the receptor types that they influence, though most of them also influence D2 receptors, although not as strongly as the typical antipsychotics. These newer antipsychotics are not necessarily more helpful for schizophrenia, but they have fewer motor side effects.

First-generation antipsychotics such as haloperidol and thioridazine may produce extrapyramidal symptoms (EPS) side effects such as acute dystonia (involuntary movements including repetitive and twisting movements), akathisia (inability to sit still, often due to strong feelings of restlessness or muscle pain), cogwheel rigidity (a rigid form of muscle movement that occurs in ratchet-type jerking movements), and tardive dyskinesia (involuntary, writhing movements like grimacing, sticking out the tongue, smacking the lips, or jerking neck movements). Once these side effects begin, over time, some can become permanent; they can also interfere with the ability to work or carry out daily functioning. As you might imagine, given the existing stereotypes of schizophrenia spectrum disorders, the addition of these types of motor dysfunctions usually increases the stigma against the person, causing others to avoid them even more and increasing social isolation. As noted, some of these extrapyramidal symptoms (EPS) effects can also be painful. Once extrapyramidal symptoms (EPS) symptoms begin, lowering the antipsychotic dose may reduce the severity of the side effects; anticholinergic medications such as benztropine and biperiden may be added to the treatment regimen to reduce EPS side effects.^[3]These side effects can be a major reason why patients may stop taking their medications, leading to relapse as a result.

Second-generation, atypical antipsychotics (SGAs) are usually prescribed in treating schizophrenia, although clozapine is not recommended as a first-line treatment because of the increased risk of agranulocytosis (severe drop in white blood cell counts, potentially leading to infections and death). Second-generation, atypical antipsychotics (SGAs) have fewer extrapyramidal symptoms than typical antipsychotics, but they may have metabolic side effects, such as weight gain, hyperlipidemia (e.g. high cholesterol), and diabetes mellitus. These side effects may cause other medical concerns that contribute to the greater risk for cardiovascular mortality in patients with schizophrenia.^[4]

Nonpharmacological Therapies

Goals for the treatment of schizophrenia include identifying symptoms, increasing functioning, and preventing relapse. Typically, pharmacological and non-pharmacological treatments are combined in order to help improve daily functioning and symptom management, each of them targeting their own symptoms and areas of functioning. For example, medications are used to reduce positive and sometimes negative symptoms or to manage side effects while psychotherapeutic approaches aim to improve coping skills, symptom management, daily functioning, socialization, and the ability to work and manage one’s own life. Consider the typical age of onset for schizophrenia, for example. It usually manifests in the early years of adulthood as the brain finishing maturing. Thus, the disorder often interferes directly with learning and maintaining vital skills for autonomy and living, including managing finances, establishing relationships and families, living on one’s own, finding work and a career, and many more essential skills. Psychotherapeutic approaches seek to teach or re-teach coping and illness management skills and other skills of daily living and include cognitive enhancement therapy, individual, and group therapy.

Even a brief yet major psychotic episode can be highly disruptive to the livelihood and functioning of an individual and his/her family and friends. Psychotherapeutic management would involve medically informing the patient and their family about the condition and treatment modalities employed for the particular patient. Along with emphasizing reintegration into the societal milieu, it is essential to focus on managing comorbid disorders or stressors and improving overall coping skills. These therapies can be delivered in both individual and group settings once the person’s active symptoms have been stabilized.

In individual treatment, the person is the focus of the treatment and has all the attention and interaction with the therapist; insight-oriented therapies often are not effective if the person has ongoing symptoms since abstract thinking and planning are significantly impaired; some forms of individual therapy may be helpful if a person achieves significant remission. A group setting, although time and focus is divided, can be a beneficial form of therapy as individuals often can find support and comfort in hearing the stories of individuals with similar experiences and form friendships based on healing and a deep understanding.

Other support services for education, employment, and housing are usually offered for those with schizophrenia. For people suffering from severe schizophrenia and discharged from a stay in the hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transportation. This approach is known as assertive community treatment (ACT) and has been shown to achieve positive results in symptoms, social functioning, and quality of life. Another more intense approach is known as intensive care management (ICM). Intensive care management (ICM) is a stage further than assertive community treatment (ACT) and emphasizes support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that intensive care management (ICM) improves many of the relevant outcomes including social functioning.

Cognitive-Behavioral Therapy

In long-term psychoses and schizophrenia, CBT is used to complement medication and is adapted to meet individual needs. Interventions particularly related to these conditions include exploring reality testing (evaluating one’s own thinking and beliefs to see how well they match the actual environment), changing delusions and hallucinations, examining factors that precipitate relapse (particularly related to stress, interpersonal conflicts, and treatment resistance), and managing relapses. While several meta-analyses suggested that CBT is effective in schizophrenia, other studies contradict these findings.^[5]

Cognitive Enhancement Therapy (CET)

The evidence that cognitive deficits also contribute to functional impairment in schizophrenia has led to an increased search for treatments that might enhance cognitive function in schizophrenia. Unfortunately, as of yet, there are no pharmacological treatments that work consistently to improve cognition in schizophrenia, though many new types of drugs are currently under exploration. However, there is a type of psychological intervention, referred to as cognitive remediation, which has shown some evidence of boosting cognitive functioning in schizophrenia.

In particular, a version of this treatment called cognitive enhancement therapy (CET) has been shown to improve cognition, functional outcome, social cognition, and protection against gray matter loss (Eack et al., 2009; Eack, Greenwald, Hogarty, & Keshavan, 2010; Eack et al., 2010; Eack, Pogue-Geile, Greenwald, Hogarty, & Keshavan, 2010; Hogarty, Greenwald, & Eack, 2006) in young individuals with schizophrenia. The treatment was designed for persons whose positive and negative symptoms have been stabilized but who still struggle to function well socially and vocationally. It works by having individuals participate in structured group and computer-based exercises, with the goal of improving socialization skills and cognitive functioning (e.g., mental stamina and information processing).^[6] The development of new treatments such as cognitive enhancement therapy (CET) provides some hope that we will be able to develop new and better approaches to improving the lives of individuals with this serious mental health condition and potentially even prevent it someday.

Third-wave-approaches are new developments in CBT that emphasize the importance of acceptance, mindfulness, and emotions, the therapeutic relationship, values, goals, and meta‐cognition (Hayes & Hofmann, 2017). In psychosis, adaptations of mindfulness-based therapy, acceptance and commitment therapy (ACT) and compassion-focused therapy (CFT) have been studied most. In order to ease distress and achieve acceptance as well as to support the regaining of control, mindfulness-based interventions for psychosis guide patients to notice sensations and their own emotional and cognitive reactions to them with awareness (Chadwick, 2014). In meditation-based practices, patients learn to observe their thoughts, feelings, and symptoms in an accepting and non-judgmental way. Mindfulness interventions for psychosis have been implemented as single treatments (e.g. Chadwick, 2014) or combined with CBT (e.g. Wright et al., 2014).

In acceptance and commitment therapy (ACT) (Hayes, Strosahl, & Wilson, 1999), experiential avoidance (avoiding one’s feelings or avoiding taking productive actions) and cognitive fusion (having behavior driven by one’s thoughts without questioning the validity of one’s assumptions or beliefs) are suggested to be the core processes of suffering. In order to increase psychological flexibility and reduce distress associated with psychotic symptoms, patients are guided to develop a balance between committed value-guided action when solving actual problems and acceptance when control of thoughts and feelings is limited (e.g., in the case of hallucinations). Acceptance and commitment therapy (ACT) has been adapted for the treatment of psychosis (O’Donoghue, Morris, Oliver, Johns, & Hayes, 2018; combined with CBT, Wright et al., 2014).

Compassion-focused therapy (CFT) (Gilbert & Procter, 2006) encourages patients to be more compassionate towards themselves and others while reducing shame and self-criticism. Compassionate mind training includes appreciation and imagery exercises as well as aspects of mindfulness and aids the patient to experience different aspects of compassion in order to promote mental wellbeing. Compassion-focused therapy (CFT) has also been adapted for the treatment of psychosis (Brähler, Harper, & Gilbert, 2013).

Metacognitive training (MCT) (Moritz & Woodward, 2007) was designed to address positive symptoms in patients with schizophrenia. As cognitive biases have been related to positive symptoms (e.g., jumping to conclusions or externalizing attributional bias—assuming the motivations of others, see Garety & Freeman, 1999), metacognitive training (MCT) aims to extend the patient’s knowledge of cognitive biases and to provide corrective experiences. Implementing a wide range of examples and exercises, patients participating in metacognitive training (MCT) group training are encouraged to identify and gain insight into these cognitive biases and reduce conviction in delusional ideas. MCT is mainly administered in group format.

Social skills training (SST) builds on the observation that patients with psychotic disorders tend to show impaired social skills. Social skills training (SST) involve therapist modeling and instructing socially confident behavior in specific situations combined with role plays. Patients receive supportive feedback from the therapist and video feedback can also be used. During the end of the training that usually takes place in group format, patients are encouraged to practice the newly learned skills in daily life.^[7]