Treatment principles

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Treatment principles

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Treatment principles
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The progression of schizophrenia and functional decline
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In most patients, the formal onset of schizophrenia is preceded by a period of symptoms, known as the prodromal period.[Lieberman et al., 2001] Symptoms in this stage can include mood disturbances and cognitive symptoms, as well as positive symptoms.[Lieberman et al., 2001; McGlashan, 1996] Treatment with antipsychotic therapy can ameliorate psychotic symptoms, and maintenance therapy is effective in preventing relapse.[Lieberman et al., 2001] Because the clinical deterioration of schizophrenia may begin in the prodromal phase, early identification is important to allow timely intervention.[Lieberman et al., 2001; McGlashan, 1996]

Lieberman JA, Perkins D, Belger A, et al. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry 2001; 50 (11): 884–897.

McGlashan TH. Early detection and intervention in schizophrenia: research. Schizophr Bull 1996; 22 (2): 327–345.

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Treatment should be optimised for each individual in order to improve the outcome
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Key message: Treatment outcomes can be optimised for an individual by skilful utilisation and coordination of pharmacological, psychosocial, and educational resources.

Background
A clinically effective treatment is characterised by:[Tandon et al., 2006]

  • long-term reduction in symptoms of disease, treatment burden (adverse events), and impact of the disease on the patient and members of his or her social circle
  • sustained adherence by the patient to the prescribed treatment regimen
  • long-term increase in healthy behaviours and restoration of wellness

Skilful utilisation and coordination of available pharmacological, psychosocial, and educational resources targeted to each patient’s personal situation, goals, and current phase of illness can ultimately maximise clinical effectiveness across all four of the outcome domains (symptoms of disease, treatment burden, disease burden, and overall health and wellness).[Tandon et al., 2006]

A recovery orientation, along with a culture of setting specific treatment goals, selecting treatments with a larger evidence base, and monitoring the individual patient’s response to treatment in a reliable and explicit manner serve to minimise disease burden (while adding minimal treatment burden) in order to maximise the health and wellness of the individual patient.[Tandon et al., 2006]

 

Tandon R, Targum SD, Nasrallah HA, et al. Strategies for maximizing clinical effectiveness in the treatment of schizophrenia. J Psychiatr Pract 2006; 12 (6): 348–363.

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Psychosocial interventions should be tailored to the goals, needs, abilities and circumstances of patients
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Key message: Psychosocial interventions should be tailored to the carefully assessed goals, needs, abilities, and circumstances of individuals rather than assuming a ‘one size fits all’ approach.

Background

  • Psychosocial interventions work synergistically with medication to optimise treatment adherence and successful community living.[CPA, 2005]
  • Optimal management requires the integration of medical and psychosocial interventions.[CPA, 2005] Such interventions should not be seen as competing approaches but, in most cases, as necessary complementary interventions to improve clinical symptoms, functional outcome and quality of life.[CPA, 2005]
  • Effective psychosocial interventions may improve medication adherence, reduce risk of relapse and the need for readmission to hospital, reduce distress resulting from symptoms, improve functioning and quality of life, and provide support for patients, their families and caregivers.[CPA, 2005]
  • Common comorbid conditions such as substance abuse, anxiety disorders, and depression need to be recognised and addressed with psychosocial interventions.[CPA, 2005]

 

Canadian Psychiatric Association. Clinical practice guidelines. Treatment of schizophrenia. Can J Psychiatry 2005; 50 (13 Suppl. 1): 7S–57S.

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Disease phases in schizophrenia
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The slide summarises the main phases of schizophrenia, and the frequency of patients transitioning between phases based on a wide-ranging literature review.[Carbon & Correll, 2014] After reviewing the literature, the authors conclude that a key problem in understanding the course of schizophrenia is the differences in definitions and concepts used to identify the various stages.[Carbon & Correll, 2014] However, the review did identify the duration of untreated psychosis as a modifiable risk factor that clinicians can act upon now, as well as nonadherence to antipsychotic medications, and certain comorbidities.[Carbon & Correll, 2014]

Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci 2014; 16 (4): 505–524.

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Different phases of schizophrenia have different treatment goals
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According to the American Psychiatric Association guidelines on the treatment of schizophrenia, the goals of treatment are adapted to the stage of the illness.[Lehman et al., 2010]

Acute phase
The goals of treatment during the acute phase of a psychotic exacerbation are to prevent harm, control disturbed behaviour, reduce the severity of psychosis and associated symptoms (e.g., agitation, aggression, negative symptoms, affective symptoms), determine and address the factors that led to the occurrence of the acute episode, effect a rapid return to the best level of functioning, develop an alliance with the patient and family, formulate short- and long-term treatment plans, and connect the patient with appropriate aftercare in the community.[Lehman et al., 2010]

Stabilisation phase
During the stabilisation phase, the aims of treatment are to sustain symptom remission or control, minimise stress on the patient, provide support to minimise the likelihood of relapse, enhance the patient’s adaptation to life in the community, facilitate the continued reduction in symptoms and consolidate remission, and promote the process of recovery.[Lehman et al., 2010]

Stable phase
Treatment during the stable phase is designed to sustain symptom remission or control, minimise the risk and consequences of relapse, and optimise functioning and the process of recovery.[Lehman et al., 2010]

Lehman AF, Lieberman JA, Dixon LB, et al.; American Psychiatric Association: steering committee on practice guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161 (2 Suppl.): 1–56.

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Factors to consider when setting treatment goals
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Because schizophrenia is a chronic illness that influences virtually all aspects of life of the affected persons, treatment planning has three goals:[Lehman et al., 2010]

  1. reduce or eliminate symptoms
  2. maximise quality of life and adaptive functioning
  3. promote and maintain recovery from the debilitating effects of illness to the maximum extent possible.

Accurate diagnosis has enormous implications for short- and long-term treatment planning, and it is essential to note that diagnosis is a process rather than a one-time event.[Lehman et al., 2010] As new information becomes available about the patient and his or her symptoms, the patient’s diagnosis should be re-evaluated, and, if necessary, the treatment plan should be changed.[Lehman et al., 2010]

Lehman AF, Lieberman JA, Dixon LB, et al.; American Psychiatric Association: steering committee on practice guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161 (2 Suppl.): 1–56.

Other reference used on slide
Oh J, Ko YH, Paik JW, et al. Variables influencing subjective well-being in patients with schizophrenia. Korean J Schizophr Res 2014; 17 (2): 93–99.

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The importance of relapse prevention
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As shown on the slide, there are many functional consequences of relapse, including long-term disability, an increased risk of suicide, decline in cognitive function, and decreased quality of life.[Ascher-Svanum et al., 2010; Birchwood et al., 2000; Briggs et al., 2008; Lieberman et al., 2008; Kane, 2007]

It is increasingly clear that patients with schizophrenia are a heterogenous group in each domain of recovery.[Lieberman et al., 2008] A limitation of the current approach to therapy is the lack of a consistent and specific terminology to allow communication between advocates, researchers, and policy makers.[Lieberman et al., 2008] Coupled with the current incomplete understanding of the pathophysiology of schizophrenia, this has led some to pessimistically predict that in the immediate future, therapies are likely to be restorative for some patients, ameliorative for most, but ineffective for some.[Lieberman et al., 2008]

Ascher-Svanum H, Zhu B, Faries DE, et al. The cost of relapse and the predictors of relapse in the treatment of schizophrenia. BMC Psychiatry 2010; 10: 2.

Birchwood M, Spencer E, McGovern D. Schizophrenia: early warning signs. Adv Psychiatr Treat 2000; 6 (2): 93–101.

Briggs A, Wild D, Lees M, et al. Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation. Health Qual Life Outcomes 2008; 6: 105.

Kane JM. Treatment strategies to prevent relapse and encourage remission. J Clin Psychiatry 2007; 68 (Suppl. 14): 27–30.

Lieberman JA, Drake RE, Sederer LI, et al. Science and recovery in schizophrenia. Psychiatr Serv 2008; 59 (5): 487–496.

Shepherd M, Watt D, Falloon I, Smeeton N. The natural history of schizophrenia: a five-year follow-up study of outcome and prediction in a representative sample of schizophrenics. Psychol Med Monogr Suppl 1989; 15: 1–46.

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Antipsychotic therapy significantly reduces relapse rates
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A systematic review and meta-analysis, published in 2012, identified 116 reports from 65 trials of antipsychotic therapy in patients with schizophrenia.[Leucht et al., 2012] This information amounted to data for 6,493 patients.[Leucht et al., 2012] The results demonstrated that maintenance antipsychotic therapy has benefits for patients, including reduced risk of relapse, improved quality of life, and reduced aggressive acts.[Leucht et al., 2012] However, the authors caution that the benefits of antipsychotics must be weighed against the risk of adverse events.[Leucht et al., 2012]

Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379 (9831): 2063–2071.

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Continuous maintenance treatment may decrease deterioration in symptoms during the second year following diagnosis
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Key message: Continuous maintenance treatment is more effective than targeted intermittent treatment in preventing relapse.

Background
This randomised controlled trial investigated the impact of continuous maintenance treatment versus targeted intermittent treatment after stepwise discontinuation in the second year following the diagnosis of schizophrenia.[Gaebel et al., 2011]

A total of 96 first-episode patients were enrolled from the German Research Network on Schizophrenia, and 44 were assigned to treatment.[Gaebel et al., 2011]

Participants assigned to the maintenance treatment arm in the second year of the trial demonstrated lower risk of relapse and a higher survival rate from deterioration than those assigned to intermittent treatment.[Gaebel et al., 2011]

Clinical deterioration: Increase from baseline in the sum of Positive and Negative Syndrome Scale (PANSS) positive and negative scores ≥25%, or ≥10 points (if baseline value ≤40), or a Clinical Global Impression – Change (CGI-C) score ≥6.[Gaebel et al., 2011]

Mean survival time (Kaplan–Meier estimates): intermittent treatment 41.0 weeks; maintenance treatment 50.0 weeks; log rank=13.4; p<0.001.[Gaebel et al., 2011]

 

Gaebel W, Riesbeck M, Wölwer W, et al. Relapse prevention in first-episode schizophrenia –  maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia. J Clin Psychiatry 2011; 72 (2): 205–218.

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Only a small proportion of patients with schizophrenia achieve recovery
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Key message: Some patients with schizophrenia may achieve recovery with effective treatment. Social functioning, medication adherence, and type of antipsychotic, are important predictors of recovery.

Background
In a 3-year observational study of adults with schizophrenia (n=6,642), the frequency and predictors of patient outcomes were assessed.[Novick et al., 2009]

The average age at entry was 40.2 years (standard deviation: 12.9 years), and mean duration of illness was 11.8 years.[Novick et al., 2009]

Long-lasting symptomatic remission was defined as achieving a level of severity that was mild or less (i.e., a score of <4 on a scale from 1 to 7) in the Clinical Global Impression – Schizophrenia (CGI-SCH) positive, negative, cognitive, and overall severity scores, plus no inpatient admission for a minimum period of 24 months maintained until the 36-month visit:[Novick et al., 2009]

  • Approximately 33% achieved long-lasting symptomatic remission.

Long-lasting adequate quality of life was defined as achieving an EuroQoL5 dimensions visual analogue scale (EQ-5D VAS) score ≥70 for a minimum period of 24 months and maintaining it until the 36-month visit:[Novick et al., 2009]

  • Approximately 27% achieved long-lasting adequate quality of life.

Long-lasting functional remission was defined as fulfilling the following three criteria for a minimum period of 24 months and maintaining  them until the 36-month visit: (1) a positive occupational/vocational status (i.e., paid or unpaid full- or part-time employment, being an active student, or being a housewife); (2) living independently; and (3) having active social interactions (i.e., having more than one social contact during the past 4 weeks or having a spouse or partner):[Novick et al., 2009]

  • Approximately 13% achieved long-lasting functional remission.

Although the results should be interpreted conservatively because of the observational, non-randomised study design, they indicate that only a small proportion of patients with schizophrenia achieve recovery.[Novick et al., 2009]

 

Novick D, Haro JM, Suarez D, et al. Recovery in the outpatient setting: 36-month results from the Schizophrenia Outpatients Health Outcomes (SOHO) study. Schizophr Res 2009; 108 (1–3): 223–230.

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Selecting the most suitable treatment – minimal adverse events and maximum adherence
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Selecting suitable treatments for schizophrenia can pose a dilemma for psychiatrists
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Please note, this slide builds

Key message: When selecting treatments for schizophrenia, physicians have to consider many variables, including the patient’s health and lifestyle, co-prescribed medications, and previously experienced adverse events.

Background
In selecting treatments for schizophrenia, clinicians have to consider variables related to the patient (e.g., age, history of response), the illness (e.g., duration, symptom type, comorbidity), the medication (e.g., pharmacodynamics, pharmacokinetics, efficacy, tolerability, cost) and the patient’s environment.[Kane & Correll, 2010; Correll, 2011]

The ideal antipsychotic would:[Correll, 2011]

  • Reduce excess dopamine levels in the mesolimbic pathway and/or associative striatum to treat psychosis, while maintaining adequate dopamine levels where dopamine is needed.
  • Cause minimal histaminergic blockade (associated with sedation, weight gain, and metabolic complications), cholinergic blockade (associated with dry mouth, constipation and impaired cognition), and α1-adrenergic blockade (associated with orthostasis).
  • Have a sufficiently broad gap between efficacy and toxicity, so that dosing could be increased as needed without triggering excessive adverse events.
  • Have efficacy for depression and anxiety.
  • Cause no or minimal extrapyramidal symptoms (EPS) and akathisia, and have little risk of tardive dyskinesia (TD).
  • Be weight-neutral, cause no metabolic abnormalities, and reverse weight gain and/or lipid abnormalities.

Kane JM, Correll CU. Pharmacologic treatment of schizophrenia. Dialogues Clin Neurosci 2010; 12 (3): 345–357.

Correll CU. What are we looking for in new antipsychotics? J Clin Psychiatry 2011; 72 (Suppl. 1): 9–13.

Other references used on slide
Abidi S, Bhaskara SM. From chlorpromazine to clozapine – antipsychotic adverse effects and the clinician’s dilemma. Can J Psychiatry 2003; 48 (11): 749–755.

Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382 (9896): 951–962.

Uçok A, Gaebel W. Side effects of atypical antipsychotics: a brief overview. World Psychiatry 2008; 7 (1): 58–62.

Barnes TR; Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2011; 25 (5): 567–620.

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Guidelines for good practice are measurement-based and individualised
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Key message: Guidelines for the treatment of schizophrenia recommend regular monitoring for adverse events and efficacy of treatment.

Background

  • Symptoms (mental and physical), signs, activities of daily living (ADL), level of functioning, and adverse events are key areas to assess at all phases of the illness.[CPA, 2005]
  • Collateral information (e.g., from family members, caregivers and healthcare professionals) is usually essential for a more complete understanding of symptoms, signs and functioning.[CPA, 2005]
  • Longitudinal follow-up by the same clinician(s) to monitor improvements or worsening is optimal.[CPA, 2005]
  • The patient’s competency to accept or refuse treatment must be periodically assessed and recorded.[CPA, 2005]
  • Regular and ongoing evaluations are equally necessary when patients respond to medications, when they fail to respond, and when they develop adverse events.[CPA, 2005] Standardised scales are useful tools for baseline and later assessments.[CPA, 2005]
  • Patients will often not spontaneously bring complaints and information to clinicians, and therefore, active, specific questioning, and informed examination and investigation are usually necessary.[CPA, 2005]
  • Medications must be individualised because the individual response is highly variable.[CPA, 2005]
  • Patients must be involved in decisions and choices for pharmacotherapy.[CPA, 2005]

Canadian Psychiatric Association. Clinical practice guidelines. Treatment of schizophrenia. Can J Psychiatry 2005; 50 (13 Suppl. 1): 7S–57S.

Other references used on slide
Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161 (Suppl. 2): 1–56.

Hasan A, Falkai P, Wobrock T, et al.; WFSBP Task force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 2013; 14 (1): 2–44.

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Treatment of schizophrenia needs a rational approach with minimal tolerability issues to optimise patient functioning
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Please note, this slide builds

Key message: There is a need for a rational approach to the management of schizophrenia. Treatment guidelines recommend choosing a medication that offers good clinical response without intolerable adverse events, as well as regular monitoring of adverse events.

References used on slide
Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161 (Suppl. 2): 1–56.

Kuipers E, Kendall T, Udechuku AY, et al. Psychosis and schizophrenia in adults. Treatment and management. National Clinical Guideline Number 178. NICE, 2014.

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Reference used on slide
National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. National Clinical Guideline Number 178. NICE, 2014.

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Referencias

Reference used on slide
National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. National Clinical Guideline Number 178. NICE, 2014.

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Referencias

Reference used on slide
Hasan A, Falkai P, Wobrock T, et al.; World Federation of Societies of Biological Psychiatry (WFSBP) Task Force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry 2012; 13 (5): 318–378.

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Shared decision-making and patient centered care lead to better health outcomes
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Key message: Shared decision-making is a an important process, in which clinicians and patients work together to make decisions about care and treatment, and it can lead to better adherence to treatment and medication.

Background
A report, entitled “People in control of their own health and care: the state of involvement”,  produced by the King’s Fund concentrates on individual’s involvement in their own health and care, and the involvement of an individual’s family or other carers.[Foot et al., 2014]

Shared decision-making involves the following stages:[Foot et al., 2014]

  • Information exchange, in which the clinician provides reliable, evidence-based information, outlines the options, their likely outcomes, and uncertainties and risks, and the patient shares their own knowledge of the condition, and the beliefs, values and preferences that may impact on their decision.
  • Deliberation, during which the options are discussed and preferences are clarified.
  • Implementation, when the clinician and patient work together to achieve consensus, and the patient’s decisions are then recorded and implemented.

A central part of shared decision-making is the recognition that patients and clinicians bring different, but equally important, knowledge and expertise to the process.[Foot et al., 2014; Coulter & Collins, 2011]

Foot C, Gilburt H, Dunn P, et al. People in control of their own health and care: the state of involvement. The King’s Fund, 2014.

Coulter A, Collins A. Making shared decision-making a reality: no decision about me, without me. The King’s Fund, 2011.

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Efficacy for positive and negative symptoms are higher priorities than tolerability for physicians when choosing a treatment
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Please note, this slide builds

Key message: When choosing a treatment, physicians prioritise efficacy for positive and negative symptoms over tolerability.

Background

  • In a large, multinational, cross-sectional survey, psychiatrists in the US and five European countries (France, Germany, Italy, Spain and the United Kingdom) who had prescribed antipsychotics for ≥15 patients with schizophrenia within the preceding 3 months, provided data on their patients’ demographic and clinical characteristics, on their antipsychotic prescribing practices, and on drug attributes influencing treatment choice.[Lecrubier et al., 2007]
  • Data were collected from 872 physicians on 6,523 patients (85% European, 15% US).1 Most patients were aged 25–44 years, 63% were men and 66% were outpatients.[Lecrubier et al., 2007]
  • As shown on the slide, efficacy for positive symptoms, efficacy for negative symptoms, and tolerability were the top three leading reasons for physicians when choosing a particular antipsychotic medication.[Lecrubier et al., 2007]
  • Control of positive and negative symptoms was considered to be the leading unmet need of current antipsychotic treatment.[Lecrubier et al., 2007]

Note: the data in this slide are from a paper published in 2007.[Lecrubier et al., 2007] Around this time, expectations for drugs treating negative symptoms were high.[Stahl, 2006]

Lecrubier Y, Perry R, Milligan G. Physician observations and perceptions of positive and negative symptoms of schizophrenia: a multinational, cross-sectional survey. Eur Psychiatry 2007; 22 (6): 371–379.

Stahl SM. Positive findings for negative symptoms of schizophrenia: no longer untreatable? Acta Psychiatr Scand 2006; 114 (5): 301–302.

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Negative symptoms and the treatment of schizophrenia
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Negative symptoms are so called because they describe thoughts or behaviour that a person used to have, before they developed schizophrenia, but now no longer have (or have to a lesser extent).[Living with schizophrenia, 2019; Mitra et al., 2016] Essentially, negative symptoms are normal aspects of a person’s behaviour that patients with schizophrenia no longer experience.[Living with schizophrenia, 2019; Mitra et al., 2016] There are eight symptoms that are collectively called ‘negative symptoms’:[Living with schizophrenia, 2019]

  1. Apathy
  2. Absent, blunted or incongruous emotional responses
  3. Reductions in speech
  4. Social withdrawal
  5. Impaired attention
  6. Anhedonia
  7. Sexual problems
  8. Lethargy

Living with schizophrenia – negative symptoms of schizophrenia: understanding them. Available at: https://www.livingwithschizophreniauk.org/information-sheets/negative-sy.... Accessed May 2019.

Mitra S, Mahintamani T, Kavoor AR, Nizamie SH. Negative symptoms in schizophrenia. Ind Psychiatry J 2016; 25 (2): 135–144.

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Depressive symptoms and the treatment of schizophrenia
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In patients with schizophrenia, the connection between depression and cognitive performance has not been well studied, and the link between the presence of depressive symptoms and functional impairment in patients with schizophrenia is a contested one.[Harvey, 2011] Somewhat paradoxically, some have associated depressive symptoms with better social and cognitive performance.[Rieckmann et al., 2005] Taken together, though, the weight of evidence suggests that mood symptoms in patients with schizophrenia are associated with greater real-world disability.[Harvey, 2011]

Harvey PD. Mood symptoms, cognition, and everyday functioning in major depression, bipolar disorder, and schizophrenia. Innov Clin Neurosci 2011; 8 (10): 14–18.

Rieckmann N, Reichenberg A, Bowie CR, et al. Depressed mood and its functional correlates in institutionalized schizophrenia patients. Schizophr Res 2005; 77 (2–3): 179–187.

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Negative feelings towards medication are associated with lower scores in both affect and self-esteem quality of life subscales
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Key message: Negative feelings towards medication are associated with lower scores in both affect and self-esteem.

Background

  • Cross-sectional study investigating patients aged 19–60 (n=80) with schizophrenic disorder according to International Classification of Diseases 10th revision (ICD-10) criteria who had a duration of illness >1 year and whose discharge from an inpatient unit had been ≥6 weeks earlier.[Hofer et al., 2004]
  • The aim of the study was to investigate the relationship between antipsychotic-induced adverse events and subjective quality of life (QoL).[Hofer et al., 2004]
  • Various rating scales were used: Positive and Negative Syndrome Scale (PANSS), St. Hans Rating Scale for Extrapyramidal Syndromes, the UKU Side Effect Rating Scale, the Drug Attitude Inventory (DAI), and the Lancashire Quality of Life Profile.[Hofer et al., 2004]
  • The combined effects of sociodemographic variables, psychopathology, type of antipsychotic medication, antipsychotic-induced adverse events, and attitude toward medication, on QoL were analysed with multiple linear regression analysis (summarised on the slide).[Hofer et al., 2004]

 

Hofer A, Kemmler G, Eder U, et al. Quality of life in schizophrenia: the impact of psychopathology, attitude toward medication, and side effects. J Clin Psychiatry 2004; 65 (7): 932–939.

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Adverse events are associated with lower adherence
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Key message: Medication adverse events are highly prevalent and significantly associated with medication non-adherence.

Background

  • Data were analysed from a 2007–2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (n=876).[DiBonaventura et al., 2012]
  • Adherence to medications was assessed by using the four-item Morisky Medication Adherence Scale (MMAS). Adherence was defined as a score of zero on the MMAS.[DiBonaventura et al., 2012]
  • Medication adverse events were self-reported.[DiBonaventura et al., 2012]
  • Most of the adverse events assessed were significantly associated with a decreased likelihood of medication adherence.[DiBonaventura et al., 2012] Sensitivity analyses using the more restrictive definition of adverse event presence did not change overall model results with respect to significance or magnitude.[DiBonaventura et al., 2012]
  • EPS/agitation-related adverse events were the most strongly associated with nonadherence, and were commonly reported.[DiBonaventura et al., 2012]
  • Adverse events of antipsychotic medications are highly prevalent and significantly associated with lower adherence, which is associated with increased healthcare resource use.[DiBonaventura et al., 2012]

DiBonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry 2012; 12: 20.

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Adherence to antipsychotic therapy
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There are several lines of evidence showing that only a minority of patients with schizophrenia strictly adhere to their antipsychotic medication.[Tiihonen et al., 2011; Sendt et al., 2015; Ljungdalh, 2017] Several risk factors are associated with medication non-adherence in patients with schizophrenia, including illicit drug and alcohol use, antidepressant treatment, and greater levels of patient-reported medication-related cognitive impairment.[Ascher-Svanum et al., 2006]

One recently conducted systematic literature review of adherence rates in schizophrenia reported a wide range of adherence values ranging from 11–72%.[Ljungdalh, 2017] Part of the explanation for this range is the non-standard way in which adherence, and non-adherence, are defined and monitored in clinical trials.[Ljungdalh, 2017; Osterberg & Blaschke, 2005] This makes it challenging to develop and implement interventions to foster good adherence.[Ljungdalh, 2017; Osterberg & Blaschke, 2005]

Ascher-Svanum H, Zhu B, Faries D, et al. A prospective study of risk factors for nonadherence with antipsychotic medication in the treatment of schizophrenia. J Clin Psychiatry 2006; 67 (7): 1114–1123.

Ljungdalh PM. Non-adherence to pharmacological treatment in schizophrenia and schizophrenia spectrum disorders – an updated systematic literature review. Eur J Psychiatry 2017; 31 (4): 172–186.

Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353 (5): 487–497.

Sendt KV, Tracy DK, Bhattacharyya S. A systematic review of factors influencing adherence to antipsychotic medication in schizophrenia-spectrum disorders. Psychiatry Res 2015; 225 (1–2): 14–30.

Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011; 168 (6): 603–609.

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The risks and consequences of non-adherence
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Only a minority of patients with schizophrenia are strictly adherent to antipsychotic medication.[Tiihonen et al., 2011; Ljungdalh, 2017] The consequences of non-adherence can be severe; because antipsychotic medications effectively reduce the risk of psychotic relapse, non-adherence increases the risk of relapse.[Zipursky et al., 2014] Indeed, in one systematic review of relapse rate in the year following a first episode of non-affective psychosis, the rate of relapse was 3% in patients taking antipsychotics, compared with 77% in patients who were not treated with antipsychotic medication.[Zipursky et al., 2014]

Ljungdalh PM. Non-adherence to pharmacological treatment in schizophrenia and schizophrenia spectrum disorders – an updated systematic literature review. Eur J Psychiatry 2017; 31 (4): 172–186.

Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011; 168 (6): 603–609.

Zipursky RB, Menezes NM, Streiner DL. Risk of symptom recurrence with medication discontinuation in first-episode psychosis: a systematic review. Schizophr Res 2014; 152 (2–3): 408–414.

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Improving adherence with LAIs can lead to improved outcomes
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A systematic review and meta-analysis, published in 2012, identified 116 reports from 65 trials of antipsychotic therapy in patients with schizophrenia.[Leucht et al., 2012] This information amounted to data for 6,493 patients.[Leucht et al., 2012] The results demonstrated that maintenance antipsychotic therapy has benefits for patients, including reduced risk of relapse, improved quality of life, and reduced aggressive acts.[Leucht et al., 2012] However, the authors caution that the benefits of antipsychotic treatment must be weighed against the risk of adverse events.[Leucht et al., 2012]

Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379 (9831): 2063–2071.

Other references used on slide
Kishimoto T, Hagi K, Nitta M, et al. Effectiveness of long-acting injectable vs oral antipsychotics in patients with schizophrenia: a meta-analysis of prospective and retrospective cohort studies. Schizophr Bull 2018; 44 (3): 603–619.

Kishimoto T, Nitta M, Borenstein M, et al. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry 2013; 74 (10): 957–965.

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Take home points
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Adverse events can impose a significant burden on patients
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Please note, this slide builds.

Key message: Treatment adverse events, which are reported by the majority of patients with schizophrenia, can impose a significant burden on patients, reducing quality of life and causing long-term distress if not treated.

Background
In an Australian study that combined the findings of two studies of patients with psychosis (the first in 1997–1998 [n=687], the second in 2010 [n=1,211]), 77.4% reported medication adverse events in the previous 4 weeks, 61.0% reported impairment due to medication adverse events, and 29.9% reported moderate/severe impairment due to adverse events.[Morgan et al., 2010]

The ‘Psychosis Screener’ was used for census month screening, and the ‘Diagnostic Interview for Psychosis’ was used for the interview.[Morgan et al., 2010] The proportions reporting medication adverse events and associated impairment were comparable for both survey periods.[Morgan et al., 2010] Questions from the 1997−1998 psychosis survey were included to enable an assessment of change over time.[Morgan et al., 2010]

Morgan VA, Waterreus A, Jablensky A, et al. People living with psychotic illness in 2010: the second Australian national survey of psychosis. Aust N Z J Psychiatry 2012; 46 (8): 735–752.

Other references used on slide
Awad AG, Hogan TP. Subjective response to neuroleptics and the quality of life: implications for treatment outcome. Acta Psychiatr Scand Suppl 1994; 380: 27–32.

Barnes TR; Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2011; 25 (5): 567–620.

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Adverse events can be classified into different groups
Slide information
Referencias

Please note, this slide builds.

Key message: There are many different adverse events that can be induced by antipsychotics, and these can be classified into different groups, such as sedating, activating, metabolic, etc.

Cheng-Shannon J, McGough JJ, Pataki C, McCracken JT. Second-generation antipsychotic medications in children and adolescents. J Child Adolesc Psychopharmacol 2004; 14 (3): 372–394.

Citrome L. Activating and sedating adverse effects of second-generation antipsychotics in the treatment of schizophrenia and major depressive disorder: absolute risk increase and number needed to harm. J Clin Psychopharmacol 2017; 37 (2): 138–147.

Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161 (Suppl. 2): 1–56.

Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353 (12): 1209–1223.

Kane JM, Skuban A, Hobart M, et al. Overview of short- and long-term tolerability and safety of brexpiprazole in patients with schizophrenia. Schizophr Res 2016; 174 (1–3): 93–98.

UpToDate website. Jibson MD. Second-generation antipsychotic medications: pharmacology, administration, and comparative side effects. https://www.uptodate.com/contents/second-generation-antipsychotic-medica.... Accessed April 2019.

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There are multiple clinical benefits of a low risk of extrapyramidal symptoms
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Referencias

Key message: EPS adversely impact several aspects of antipsychotic efficacy and tolerability, thereby worsening the outcome for the afflicted individuals. Therefore, there are multiple clinical benefits of drugs with low risk of EPS.

Note: ‘Atypical’ (‘second generation’) antipsychotics are associated with a lower risk of EPS compared to older conventional antipsychotics, and are therefore better able to separate the therapeutic antipsychotic effect from EPS.

Background
The costs of EPS are not limited to parkinsonian motor manifestations, but extend to increased negative symptoms and cognitive impairment, more dysphoria, higher likelihood of non-compliance, and greater risk of developing tardive dyskinesia.[Tandon & Jibson, 2002]

  • Expression of EPS significantly increases the likelihood of subsequent tardive dyskinesia – tardive dyskinesia, in turn, is associated with increased morbidity and mortality.[Tandon & Jibson, 2002]
  • EPS contribute to secondary negative symptoms, increasing the severity of this symptom dimension and attendant dysfunction.[Tandon & Jibson, 2002]
  • EPS are associated with cognitive dysfunction.[Tandon & Jibson, 2002]
  • Significant EPS may be correlated with dysphoria.[Tandon & Jibson, 2002]

The primary advantage of newer agents is their superior adverse event profiles, particularly with regard to EPS.[Tandon & Jibson, 2002]

The implications of EPS reduction potentially touch virtually every domain of pathology in schizophrenia, including short- and long-term movement disorders, negative symptoms, non-compliance, relapse rate, cognitive dysfunction, and dysphoria.[Tandon & Jibson, 2002]

This EPS advantage of atypical antipsychotics is likely to lead to improved patient compliance and a superior long-term outcome in patients treated with these medications.[Tandon & Jibson, 2002]

Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 2002; 14 (2): 123–129.

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Akathisia is associated with emotional symptoms and cognitive impairment
Slide information
Referencias

Please note, this slide builds.

Key message: Akathisia is associated with emotional symptoms (e.g., reduced self-esteem, anxiety, depression and paranoid ideation) and cognitive impairment (e.g., problems with mental control, associate learning, perception and coping).

Background

  • In a cross-sectional study, 80 patients with a schizophrenic disorder (according to ICD-10 criteria) who had an illness duration of >1 year were investigated, by using various rating scales: Positive and Negative Syndrome Scale (PANSS), the St. Hans Rating Scale for EPS, the UKU Side Effect Rating Scale, the Drug Attitude Inventory, and the Lancashire Quality of Life Profile.[Hofer et al., 2004]
  • Mild to moderate akathisia was reported in 23% of all patients, and there was a significant negative correlation between akathisia (St. Hans scale) and self-esteem (-0.32, p<0.01).[Hofer et al., 2004]

 

  • In another study, 67 outpatients with schizophrenia receiving stable doses of specific antipsychotic therapies were evaluated for akathisia and other extrapyramidal adverse events.[Kim et al., 2007]
  • Subjective cognitive dysfunction was comprehensively assessed by using the Frankfurt Complaint Questionnaire (FCQ).[Kim et al., 2007]
  • The severity of subjective cognitive deficits was compared between the groups with and without akathisia.[Kim et al., 2007]
  • The akathisia group (n=25) scored significantly higher (worse) on the FCQ Total score than the non-akathisia group (n=42) (p<0.05).[Kim et al., 2007]
  • In phenomenological subscale scores, the akathisia group had significantly higher (worse) scores on various subscales, i.e., ‘anxiety’, ‘disorder of selective attention’, ‘deterioration of discrimination’, ‘perceptual disorder’ and ‘disorder of coping responses’ than the non-akathisia group (p<0.05).[Kim et al., 2007]

 

  • In a third study, 41 stable and chronic patients with schizophrenia, who were receiving maintenance antipsychotic treatment, were rated by using the Barnes Akathisia Rating Scale (BARS) for drug-induced akathisia.[Kim et al., 2002]
  • Subjective symptoms were evaluated by using the Symptom Checklist-90-Revised (SCL-90-R), and cognitive function was assessed by using the Wechsler Memory Scale (WMS).[Kim et al., 2002]
  • Analysis of covariance (ANCOVA) with relevant variables as covariates revealed that patients with akathisia (n=17) had significantly higher (worse) scores on the depression subscale of the SCL-90-R than those without akathisia (n=24) (p<0.01).3 Patients with akathisia also had significantly lower (worse) scores on the mental control subtest of the WMS (p<0.05).[Kim et al., 2002]
  • Further analysis using ordinal logistic regression revealed that the depression subscale of the SCL-90-R and the mental control subtest of the WMS were significantly associated with the severity of akathisia.[Kim et al., 2002]

Hofer A, Kemmler G, Eder U, et al. Quality of life in schizophrenia: the impact of psychopathology, attitude toward medication, and side effects. J Clin Psychiatry 2004; 65 (7): 932–939.

Kim JH, Byun HJ. Association of subjective cognitive dysfunction with akathisia in patients receiving stable doses of risperidone or haloperidol. J Clin Pharm Ther 2007; 32 (5): 461–467.

Kim JH, Lee BC, Park HJ, et al. Subjective emotional experience and cognitive impairment in drug-induced akathisia. Compr Psychiatry 2002; 43 (6): 456–462.

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Gastrointestinal adverse events can occur with antipsychotics
Slide information
Referencias

Key message: Gastrointestinal adverse events, such as constipation, can occur with antipsychotics.

Background

  • This was a retrospective study in patients with schizophrenia consecutively admitted, between 2007–2009, and treated with antipsychotic medication.[De Hert et al., 2011]
  • Various electronic patient data were linked to evaluate the prevalence and severity of constipation in patients with schizophrenia under routine treatment conditions.[De Hert et al., 2011]
  • Constipation was defined as having at least one new prescription of a laxative.[De Hert et al., 2011]
  • Over the 22-month observation period, there were 371 admissions of 273 individual patients with schizophrenia.[De Hert et al., 2011] The mean age of the sample was 40.1 years (range 17–82) and 65.6% were male.[De Hert et al., 2011]
  • Over a period of 22 months, 36.3% of patients (n=99) received a pharmacological treatment for constipation at least once.[De Hert et al., 2011]
  • On average, medication for constipation was prescribed for 273 days.1 Severe cases that were unresponsive to initial treatment, underwent plain X-ray of the abdomen.1 In 68.4% of patients, faecal impaction was found.[De Hert et al., 2011]
  • A high prevalence of constipation, often severe and needing medical intervention, was confirmed during the study period.[De Hert et al., 2011]

De Hert M, Dockx L, Bernagie C, et al. Prevalence and severity of antipsychotic related constipation in patients with schizophrenia: a retrospective descriptive study. BMC Gastroenterol 2011; 11: 17.

Other reference used on slide
MHRA Antipsychotics learning module 2015. Available at http://www.mhra.gov.uk/antipsychotics-learning-module/con155606?useSecon.... Accessed April 2019.

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Weight gain can occur with antipsychotics
Slide information
Referencias

This meta-analysis identified 257 clinical trials from a pool of 2,374 records.[Bak et al., 2014] The analysis included raw changes in weight, change in BMI (body mass index), ≥7% weight gain, ≥7% weight loss, and a separate analysis of patients who were antipsychotic naïve on entering a study.[Bak et al., 2014] Virtually all antipsychotics appeared to cause weight gain.[Bak et al., 2014] In antipsychotic-naïve patients, this weight gain was more pronounced.[Bak et al., 2014]

Bak M, Fransen A, Janssen J, et al. Almost all antipsychotics result in weight gain: a meta-analysis. PLOS One 2014; 9 (4): e94112.

Other references used on slide
Llorca PM, Lançon C, Hartry A, et al. Assessing the burden of treatment-emergent adverse events associated with atypical antipsychotic medications. BMC Psychiatry 2017; 17 (1): 67.

Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 2008; 13 (1): 27–35.

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Some antipsychotics are associated with high rates of sedating adverse events, which can worsen outcomes
Slide information
Referencias

Please note, this slide builds.

Key message: The sedative adverse events of antipsychotics may have significant consequences for patients, leading to medication non-adherence, increased risk of unintentional injury, and reduced cognitive performance and functional capacity. Sedation can have a severe impact on many aspects of patient life, such as preventing patients from gaining improvement from treatment, interfering with functioning and quality of life, and reducing adherence to medication.

Background

  • Data were analysed from a 2007‒2008 US survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (n=876).[DiBonaventura et al., 2012]
  • Adherence was defined as a score of zero on the MMAS.[DiBonaventura et al., 2012] The MMAS items include the presence or absence of the following non-adherent behaviours: forgetting to take medication, careless at times about taking medication, stopping medication when feeling better, and stopping medication when feeling worse.[DiBonaventura et al., 2012]
  • A single logistic regression model assessed the relationship between adverse-event clusters and adherence.[DiBonaventura et al., 2012]
  • The adverse-event cluster of sedation/cognition (which included sedation, difficulty thinking or concentrating, sleepiness, and dizziness) was associated with a lower likelihood of adherence – sedation/cognition (odds ratio [OR]: 0.70, p=0.033).[DiBonaventura et al., 2012]

DiBonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry 2012; 12: 20.

References used on slide
Lindberg N, Virkkunen M, Tani P, et al. Effect of a single-dose of olanzapine on sleep in healthy females and males. Int Clin Psychopharmacol 2002; 17 (4): 177–184.

Loebel AD, Siu CO, Cucchiaro JB, et al. Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia. CNS Spectr 2014; 19 (2): 197–205.

Miller DD. Atypical antipsychotics: sleep, sedation, and efficacy. Prim Care Companion J Clin Psychiatry 2004; 6 (Suppl. 2): 3–7.

Miller DD. Sedation with antipsychotics. Curr Psychiatr 2007; 6 (8): 38–51.

Said Q, Gutterman EM, Kim MS, et al. Somnolence effects of antipsychotic medications and the risk of unintentional injury. Pharmacoepidemiol Drug Saf 2008; 17 (4): 354–364.

Seeman MV. Antipsychotic-induced somnolence in mothers with schizophrenia. Psychiatr Q 2012; 83 (1): 83–89.

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Sedation impacts patient functioning and caregiver burden
Slide information
Referencias

Please note, this slide builds.

Key message: Sedation impacts on patient functioning and caregiver burden, and can lead to dissatisfaction with medication and discontinuation of treatment.

Background

  • Many patients with schizophrenia experience disturbances in their sleep–wake cycle, which may be a result of the disease itself, of pharmacotherapy, or of a comorbid sleep disorder.[Kane et al., 2008]
  • These sleep disturbances can seriously impair patient functioning, as well as quality of life.[Kane et al., 2008]
  • Most patients develop a tolerance to the sedating effects of medications after the acute phase of treatment; however, a substantial minority will continue to experience persistent sedation or somnolence, impacting on their quality of life.[Kane et al., 2008]
  • Although patients may not be able to accurately describe their symptom as persistent sedation, they may complain that they have no energy, they constantly feel tired, or that they cannot think clearly.[Kane et al., 2008]
  • Patients’ families may also indicate that patients do not want to get out of bed or participate in any activities, which may increase the burden on the caregiver.[Kane et al., 2008]

Kane JM, Sharif ZA. Atypical antipsychotics: sedation versus efficacy. J Clin Psychiatry 2008; 69 (Suppl. 1): 18–31.

Other reference used on slide
Hofstetter JR, Lysaker PH, Mayeda AR. Quality of sleep in patients with schizophrenia is associated with quality of life and coping. BMC Psychiatry 2005; 5: 13.

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Activating and sedating effects are among the most ‘bothersome’ antipsychotic adverse events
Slide information
Referencias

Key message: Activating (EPS, agitation) and sedating effects are among the most ‘bothersome’ antipsychotic adverse events, as rated by patients: 86.2% of patients with schizophrenia reported the presence of any adverse event.

Background

  • Data were analysed from a 2007–2008 US survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (n=876).[DiBonaventura et al., 2012]
  • Adverse events were defined as ‘present’ if the patient reported that the adverse event was at least ‘somewhat bothered’.[DiBonaventura et al., 2012]
  • Adherence was defined as a score of zero on the MMAS, and the relationships between adherence and health resource use were also examined.[DiBonaventura et al., 2012]
  • A majority (86.2%) of patients reported experiencing at least one adverse event due to their medication, and only 42.5% reported complete adherence.[DiBonaventura et al., 2012]
  • Most adverse events were associated with a significantly reduced likelihood of adherence.[DiBonaventura et al., 2012]
  • When grouped as adverse event clusters in a single model, EPS/agitation (OR: 0.57, p=0.0007), sedation/cognition (OR: 0.70, p=0.033), prolactin/endocrine (OR: 0.69, p=0.0342), and metabolic adverse events (OR: 0.64, p=0.0079) were all significantly related to lower rates of adherence.[DiBonaventura et al., 2012]
  • Patients who reported complete adherence to their medication were significantly less likely to report a hospitalisation for a mental health reason (OR: 0.51, p=0.0006), a hospitalisation for a non-mental health reason (OR: 0.43, p=0.0002), or an emergency room (ER) visit for a mental health reason (OR: 0.60, p=0.008).[DiBonaventura et al., 2012]

 

DiBonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry 2012; 12: 20.

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Medication adverse events can impair workplace performance and act as a barrier to entering or returning to work
Slide information
Referencias

Please note, this slide builds.

Key message: Medication adverse events can impair workplace performance, and can act as a barrier to entering or returning to work. The stigma resulting from medication adverse events leads to perceptions of laziness and addiction problems in patients with schizophrenia, and this stigma causes some patients to reduce or skip their medication.

Background

  • This study was a semi-structured focus group, conducted in Slovenia.[Novak & Švab, 2009] It included 10 inpatients (four women and six men aged 30–61 years) with schizophrenia or schizoaffective disorder with severe and remitting mental illness treated with antipsychotic medication.[Novak & Švab, 2009]
  • The aim was to obtain the patient’s personal views on how the adverse events of antipsychotic drugs contribute to the stigmatisation related to mental illness.[Novak & Švab, 2009]
  • Open-ended questions were posed about the influence of adverse events on illness disclosure, work performance, family relationships and treatment adherence.[Novak & Švab, 2009]
  • The patients felt most stigmatised in areas of employment and occupation.[Novak & Švab, 2009]
  • They repeatedly skipped or discontinued regular medication because of adverse events.[Novak & Švab, 2009]
  • A report from the ‘Work Foundation’ highlights the barriers experienced by people with schizophrenia in Germany to entering and remaining in the open labour market.[Steadman, 2015]
  • In order to gain an in-depth understanding of the impact of how the structural, economic, clinical and attitudinal barriers to employment affect people with schizophrenia, previous studies were reviewed, and in-depth interviews with people with experience of living with schizophrenia were conducted.[Steadman, 2015]
  • The opinions of professionals with expertise in the provision of health, social care and vocational rehabilitation, policy experts, and employers were also sought.[Steadman, 2015]
  • Schizophrenia often has considerable influence on an individual’s employment opportunities.[Steadman, 2015]
  • The symptoms of the illness, adverse events of the treatment and the possibility of relapse may make entering or returning to work difficult.[Steadman, 2015]
  • This is exacerbated by the onset of schizophrenia commonly occurring during the teens and early twenties – interrupting education, early career and the transition to independent living.[Steadman, 2015]
  • Illness onset can have significant implications for an individual’s employment prospects, with employers searching out employees with the best job history and qualifications.[Steadman, 2015]
  • Similarly, the gaps in employment history caused by periods of ill health may reduce an individual’s attractiveness to employers, compared with other candidates.[Steadman, 2015]

Novak L, Švab V. Antipsychotics side effects’ influence on stigma of mental illness: focus group study results. Psychiatr Danub 2009; 21 (1): 99–102.

Steadman K. Working with schizophrenia: employment, recovery and inclusion in Germany. The Work Foundation. 2015.

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Emotional and practical burdens of schizophrenia on families are intertwined
Slide information
Referencias

Key message: Emotional and practical burdens of schizophrenia on families are intertwined with feelings of frustration, anxiety, low self-esteem and helplessness occurring in the relatives of patients.

Background

  • This study set out to explore the relationship between stigma, accessibility of mental health facilities and family burden through individual interviews of patients’ relatives.[Tsang et al., 2003]
  • Ten interviewees from two outpatient psychiatric clinics were recruited and interviewed.1 Each interviewee had at least one family member receiving out-patient psychiatric services.[Tsang et al., 2003]
  • A combination of unstructured and semi-structured interviewing was used to obtain interviewees’ perceptions of burden, the importance they attached to different issues and the feelings they had about the illness.[Tsang et al., 2003]
  • Data analyses of the transcripts and interview notes (using the interpretive interview analysis method) showed that much of the burden on the patient’s family was related to stigma and to lack of mental health and rehabilitation services.[Tsang et al., 2003]
  • Consequences of this burden included social isolation of the families, difficulties experienced by patients when trying to obtain competitive employment, and financial difficulties.[Tsang et al., 2003]
  • Subjective burden resulting from social stigma included frustration, anxiety, low self-esteem and helplessness.[Tsang et al., 2003]
  • The objective and subjective burdens on families were intertwined.1 For example, when relatives had difficulty meeting practical demands, they would most likely also have had a negative emotional response; such an emotional response would in turn affect their ability to cope with practical demands (i.e., objective and subjective burden can augment each other).[Tsang et al., 2003]

Tsang HW, Tam PK, Chan F, Cheung WM. Sources of burdens on families of individuals with mental illness. Int J Rehabil Res 2003; 26 (2): 123–130.

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Take home points
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The importance of early intervention for patients with schizophrenia
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Association between DUP and symptom severity at first treatment contact
Slide information
Referencias

This critical review searched for literature concerning duration of untreated psychosis published up to 2004, finding 43 publications that were carried over into the meta-analysis.[Perkins et al., 2005]

Whilst a shorter duration of untreated psychosis was associated with greater response to antipsychotic treatment (as measured by severity of global psychopathology, positive symptoms, negative symptoms, and functional outcomes), duration of untreated psychosis was associated only with the severity of negative symptoms – not severity of global psychopathology, positive symptoms, or neurocognitive functioning.[Perkins et al., 2005]

 

Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 2005; 162 (10): 1785–1804.

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Association between DUP and treatment response
Slide information
Referencias

This critical review searched for literature concerning duration of untreated psychosis published up to 2004, finding 43 publications that were carried over into the meta-analysis.[Perkins et al., 2005]

Whilst a shorter duration of untreated psychosis was associated with greater response to antipsychotic treatment (as measured by severity of global psychopathology, positive symptoms, negative symptoms, and functional outcomes), duration of untreated psychosis was associated only with the severity of negative symptoms – not severity of global psychopathology, positive symptoms, or neurocognitive functioning.[Perkins et al., 2005]

 

Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 2005; 162 (10): 1785–1804.

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Patients with long DUP were less likely to achieve remission
Slide information
Referencias

This systematic review aimed to establish whether the duration of untreated psychosis is associated with prognosis in patients with schizophrenia.[Marshall et al., 2005] A total of 26 studies were identified that reported the relationship between duration of untreated psychosis and outcome, in prospective cohorts of patients with schizophrenia, recruited during their first episode of psychosis.[Marshall et al., 2005] The results demonstrate a convincing, albeit modest, association between the duration of untreated psychosis and a range of clinical outcomes, including remission.[Marshall et al., 2005] The authors are keen to point out that the association does not prove a direct cause – it does not prove that untreated psychosis causes poor outcomes.[Marshall et al., 2005] Rather, the two factors could be related via a third variable.[Marshall et al., 2005]

 

Marshall M, Lewis S, Lockwood A, et al. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry 2005; 62 (9): 975–983.

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Shorter DUP leads to improved outcomes in patients with first-episode schizophrenia
Slide information
Referencias

Several retrospective analyses have examined the interplay between the duration of untreated illness and subsequent treatment effectiveness in patients with schizophrenia.[Owens et al., 2010; Primavera et al., 2012]

One study reanalysed the data from the Northwick Park Study of First Episodes in the context of duration of untreated illness, finding a correlation between the duration of untreated illness and relapse rates.[Owens et al., 2010] Another study analysed clinical records of a cohort of 80 patients with schizophrenia, tabulating outcome variables such as number of hospitalisations, attempted suicide, course of illness, and GAF (Global Assessment of Functioning) scores.[Primavera et al., 2012] A shorter duration of untreated psychosis was linked to favourable course of illness, even in the very long term.[Primavera et al., 2012]

Owens DC, Johnstone EC, Miller P, et al. Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk. Br J Psychiatry 2010; 196 (4): 296–301.

Primavera D, Bandecchi C, Lepori T, et al. Does duration of untreated psychosis predict very long term outcome of schizophrenic disorders? Results of a retrospective study. Ann Gen Psychiatry 2012; 11 (1): 21.

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Early intervention services versus treatment as usual
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Referencias

This was a systematic literature review of publications comparing early intervention studies with treatment as usual, in patients with first-episode psychosis, or early phase schizophrenia.[Correll et al., 2018] Early intervention studies were defined as meeting the needs of people with early-phase psychosis – a multimodal treatment program, including several psychosocial and psychopharmacological interventions, provided from one team, in a coordinated and integrated fashion.[Correll et al., 2018] Of an initial selection of 8,935 records, 10 studies were included in the final meta-analysis.[Correll et al., 2018]

From the difference highlighted by the meta-analysis, the authors conclude that early intervention programmes are clearly superior to treatment as usual across a range of clinical outcomes, including hospitalisation, symptoms, and patient functioning.[Correll et al., 2018]

Correll CU, Galling B, Pawar A, et al. Comparison of early intervention services vs treatment as usual for early-phase psychosis: a systematic review, meta-analysis, and meta-regression. JAMA Psychiatry 2018; 75 (6): 555–565.

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Summary
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Summary
Slide information
Referencias
  • Improved patient functioning and improved quality of life are important treatment goals at all stages of schizophrenia management.[Hasan et al., 2013; Lehman et al., 2004]
  • Functional impairment may be the result of an insufficient treatment effect.[Schennach et al., 2015]
  • Sedating or activating adverse events can prevent patients from functioning at their optimal level and can negatively impact their quality of life.[Bobes et al., 2007; Kane & Sharif, 2008; Loebel et al., 2014; Hofer et al., 2004]
  • The adverse events associated with current treatments are often seen as a necessary compromise for continued symptom control.[Leucht et al., 2013; Barnes, 2011; Abidi & Bhaskara, 2003]
  • The limitations of current treatments, e.g., the adverse event burden, can be frustrating for all involved and can decrease quality of life.[Awad & Voruganti, 2008; Naber & Kasper, 2000; NAMI, 2008; Tsang et al., 2003]

Hasan A, Falkai P, Wobrock T, et al.; WFSBP Task force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 2013; 14 (1): 2–44.

Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161 (Suppl. 2): 1–56.

Schennach R, Riedel M, Obermeier M, et al. What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial. Eur Arch Psychiatry Clin Neurosci 2015; 265 (2): 107–116.

Bobes J, Garcia-Portilla MP, Bascaran MT, et al. Quality of life in schizophrenic patients. Dialogues Clin Neurosci 2007; 9 (2): 215–226.

Kane JM, Sharif ZA. Atypical antipsychotics: sedation versus efficacy. J Clin Psychiatry 2008; (69 Suppl. 1): 18–31.

Loebel AD, Siu CO, Cucchiaro JB, et al. Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia. CNS Spectr 2014; 19 (2): 197–205.

Hofer A, Kemmler G, Eder U, et al. Quality of life in schizophrenia: the impact of psychopathology, attitude toward medication, and side effects. J Clin Psychiatry 2004; 65 (7): 932–939.

Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382 (9896): 951–962.

Barnes TR; Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2011; 25 (5): 567–620.

Abidi S, Bhaskara SM. From chlorpromazine to clozapine – antipsychotic adverse effects and the clinician’s dilemma. Can J Psychiatry 2003; 48 (11): 749–755.

Awad AG, Voruganti LN. The burden of schizophrenia on caregivers: a review. Pharmacoeconomics 2008; 26 (2): 149–162.

Naber D, Kasper S. The importance of treatment acceptability to patients. Int J Psychiatry Clin Pract 2000; 4 (1): 25–34.

National Alliance on Mental Illness (NAMI). Schizophrenia: public attitudes, personal needs: views from people living with schizophrenia, caregivers, and the general public. Arlington, VA: NAMI, 2008.

Tsang HW, Tam PK, Chan F, Cheung WM. Sources of burdens on families of individuals with mental illness. Int J Rehabil Res 2003; 26 (2): 123–130.

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