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Clinical practice in early psychosis Managing incomplete recovery
during first episode psychosis
Introduction
While the vast majority of young people who
resistance. Thus concerted effort is required to develop a first episode of psychosis respond well address incomplete recovery from psychosis to initial treatment and have a remission of their early. These will consider the contribution of symptoms, some young people will continue illness-, person- and treatment-related factors to experience symptoms and thus show signs to the observed poor response to treatment, of early treatment resistance. Because early and suggest treatment modifications to achieve treatment response is thought to be one of the recovery as soon as possible.
strongest predictors of subsequent outcome,1,2 preventing enduring symptoms of psychosis This clinical practice point is designed and associated impaired social functioning to help clinicians understand: should be the primary aim of treatment for • why it is important to address first episode psychosis (FEP).
incomplete recovery Prolonged recovery during the early phases of • the principles for effective treatment psychotic illness may have important biological • how to use evidence-based and psychosocial consequences, such as: pharmacological and psychological ongoing disruption to social, interpersonal and strategies to address incomplete vocational functioning; demoralisation due to recovery in everyday clinical practice.
the experience of powerlessness, fear, isolation; and development of continued treatment What is incomplete recovery?
As clinicians, you always Failure to respond to treatment for psychosis has been traditionally referred to as ‘treatment resistance'. want to minimise the distress Research in this field has been hampered by a lack of of psychotic symptoms [for consistent definitions of the concept and validated assessment instruments. The term ‘treatment young people] … this means resistance' has been used particularly to describe actively managing incomplete failure of positive psychotic symptoms to remit following pharmacological treatment with antipsychotic medication. This narrow focus on positive symptoms Senior Clinician has stemmed from the traditionally poor recognition EPPIC, Orygen Youth Health Clinical Program of other symptoms that affect outcome in psychosis (e.g. cognitive symptoms) or the belief that certain Clinical experience has shown that managing symptom domains were unresponsive to medication long-term persistent psychosis or treatment resistance (e.g. negative symptoms). Hence treatment response is challenging and not always successful so focusing has been, in the past, largely evaluated on the basis of on early incomplete recovery is paramount to maximise effect on positive symptoms, which is a limited view recovery and avoid persistent illness. This is achieved that ignores important outcome dimensions like social by identifying non-adherence, adapting and and vocational functioning.3 augmenting treatment regimens as early as possible using individually-focused, comprehensive assessment However, as treatment outcome goals in psychosis and formulation.
research have broadened to include functional recovery and quality of life, the definition of treatment response and resistance have been reviewed and modified, and the term ‘incomplete recovery' was deemed more Identifying non-adherence,
'Clinically, the broader notion of ‘incomplete recovery' adapting and augmenting
may be useful, as it acknowledges the presence of disability in functional and psychosocial aspects that treatment regimens early
is persistent despite adequate treatment, referring to psychotherapeutic and psychosocial interventions as using individually-focused,
well as antipsychotic medication. Further, unlike the comprehensive assessment
rather negative label of ‘treatment resistance', the term ‘incomplete recovery' also recognises the potential and formulation can help
for a better therapeutic outcome.'4 manage incomplete recovery.
It is important to note that there are two types of incomplete recovery: 1. Treatment resistance, which refers to situations where people are receiving appropriate evidence- The prevalence and predictors
based treatments but are inadequately responding to the treatments and consequently have persistent of incomplete recovery
symptoms and disability.
The reported prevalence of incomplete recovery from 2. Resistance to treatment, which refers to the first episode psychosis (FEP) varies (due to varying situations where people have access to treatment definitions) but estimates range between 5–45%.3 but are non-adherent or are disengaged.
For schizophrenia specifically, it is estimated that 20–30% of individuals do not respond sufficiently This description highlights the importance of to an initial trial of antipsychotic trial8 and treatment considering treatment engagement and adherence resistance at 12 months is evident in at least 10% when incomplete recovery is observed. Both types of incomplete recovery need to be addressed in order to maximise rates of recovery Research has found the following risk factors in young people with early psychosis.
of incomplete recovery from FEP:10• longer untreated duration of psychosis (DUP)• poorer premorbid functioning The importance of addressing
• severe symptoms • ongoing substance abuse It is crucial to address incomplete recovery in early • cognitive deficits psychosis because there is evidence that links early treatment response to favourable outcomes. For example, evidence suggests that early recognition • non-adherence with medication of treatment resistance and subsequent treatment • poor response in first 6–12 weeks adaptation are related to a greater likelihood of remission,5 and that remission at 3 months of both • disengagement from the early psychosis service positive and negative psychotic symptoms is related • male gender.
to good functional recovery at 2 year follow-up.6 Further, early response to treatment is the strongest Encouragingly, there is evidence that engagement predictor of remission and recovery in first episode with a comprehensive early psychosis treatment service is a good prognostic indicator.11 Principles for managing incomplete
Interventions for incomplete recovery
recovery in FEP
Based on the principles outlined above, a range of There are a number of broad principles that clinicians strategies are used to manage incomplete recovery can use to manage incomplete recovery. These are from FEP. These will be described in further detail based on the fundamental principles of the early below, along with appropriate examples or practical psychosis model. A key principle is for services tips where possible.
to work to reduce DUP because research has demonstrated that this will reduce the prevalence of Prioritise engagement with the young person
incomplete recovery. Promoting early identification Establishing a good therapeutic relationship with young of psychosis, and providing easy and rapid access to people is fundamental in successfully treating early appropriate services are mechanisms for reducing DUP. psychosis. This is particularly important where recovery Once a person is linked into an early psychosis service, is slow or incomplete. These young people may have it is essential that the service is able to assess and more difficulty than usual in engaging with the treating begin treatment without delay.
team due to ongoing symptoms or social or cultural barriers that may also be influencing their recovery. Significant efforts need to be made by clinicians to Incomplete recovery should be engage young people who are experiencing incomplete identified as early as possible, ideally recovery so that they can develop a collaborative by 3 months after commencing shared understanding of the factors contributing treatment. This allows clinicians to consider to their mental ill-health.
the situation prior to symptoms becoming entrenched and the potential to avoid possible toxic effects of ongoing psychosis. Young Case scenario: Maha
people who continue to experience psychotic symptoms after 3 months of treatment should Maha, a 21-year-old female of Iranian be identified in case review and/or supervision background, has been coming to the service meetings, and plans made for review and for 5 months. She continues to experience auditory hallucinations and believes that she is being monitored by cameras in her house and neighbourhood. Maha has been very guarded in therapy sessions and unwilling to discuss the As with all cases of early psychosis, but especially nature of her auditory hallucinations, merely where there is slower than expected recovery, it is nodding in agreement to the question ‘Do you essential to instil hope and convey a sense of optimism that things will improve. Demoralisation in the face of continuing psychosis is a significant risk and Slowly, Maha's case manager began to build a complicates recovery-focused treatment.
rapport with her by being warm and interested in her life. They discussed Maha's relationship After detection of incomplete recovery, a comprehensive with her recently-deceased mother. Eventually, review of the case assessment and formulation should Maha was able to disclose that she was hearing be undertaken with the aim of gaining a thorough her mother's voice telling her not to take her and extensive understanding of the young person, medication as it would make her sick, and not their history, their experience of treatment to date, to talk to mental health workers because they their social and cultural contexts, and their hopes were untrustworthy. Maha revealed that she and aspirations. It is important to look for, and treat had never taken her prescribed antipsychotic any comorbidities, and check that all appropriate investigations have been conducted. This enables a review of diagnosis and the adequacy of the After psychoeducation about the nature treatment provided so far, and to ensure that any illness of psychotic symptoms using first-person factors or barriers to treatment effectiveness can be accounts, Maha accepted her case manager's identified and addressed. Special consideration of suggestion of a carefully monitored, 3-month substance use is important as this is a very common trial of antipsychotic medication.
factor in incomplete recovery from FEP.
Similarly, the crucial role of family and other social Ensure that the appropriate
connections in supporting a young person's recovery pharmacotherapy is being used
should be remembered. Clinicians need to engage with It is important to review the use of antipsychotic families, friends and other significant supports to enlist medication when considering incomplete recovery. their help to understand the young person's difficulties Medication that the young person has been prescribed and strengths. These strengths can then be harnessed for psychosis and its effectiveness needs to be with the support from family and friends.
reviewed to ensure that they have received adequate doses of appropriate medication. It is recommended Ensure a thorough assessment
that young people with FEP are prescribed an initial has been completed
second generation antipsychotic medication (SGA) Detecting incomplete recovery should be a trigger for 6 weeks and then, if psychotic symptoms have not for a comprehensive review of the initial assessment remitted, switched to another SGA. For a more detailed of the young person and their progress to date. explanation of the recommended pharmacological This will include ensuring that all appropriate treatments in FEP, please see the ENSP manual: physical investigations have been conducted and Medical management in early psychosis: a guide results reviewed to eliminate any physical cause for medical practitioners. for psychosis. Psychometric testing may assist in understanding the young person, and it is essential that Target medication non-adherence
a thorough understanding of the young person's social It is important to review young people's adherence circumstance, including family functioning is obtained. to their medication regimen when managing Similarly, a detailed developmental history is required incomplete recovery because non-adherence with so that a complete picture of the young person's pharmacotherapy is extremely common in all branches situation can inform decisions about interventions across the entire biopsychosocial spectrum. Finally, the diagnosis and therefore the appropriateness of Non-adherence with pharmacotherapy has particular treatments prescribed to date should be reviewed risks in psychosis and is often the reason behind following comprehensive evaluation of the cases of incomplete recovery, as illustrated in the case example of Maha above. Considerable research has been devoted to trying to find ways to improve adherence with prescribed medications, and is a topic that receives less time and attention from clinicians When incomplete recovery has been detected it is important that than it warrants. A range of factors have been shown to influence medication adherence (see Table 1), clinicians ensure a comprehensive and it is important to consider each individual's biopsychosocial assessment has been situation when choosing interventions. Collaborating conducted. This should be reviewed, with young people using a shared decision-making updated and improved to allow treatment approach to de-stigmatise mental health treatment recommendations to be re-evaluated.
and empowering them to take responsibility for their wellbeing is an important part of effectively managing Table 1. Factors associated with non-adherence to medication in psychotic illness12-14
Beliefs about treatment Service contact frequency Past experiences Continuity of care spontaneous remission Medication efficacy Adherence monitoring Access to different Cognitive function Therapeutic alliance Interventions for non-adherence fall into two broad However, there is ongoing debate about the efficacy of categories: pharmacological and psychosocial.
LAIs with recent evidence from randomised controlled trials failing to indicate a superiority of LAIs over oral medication in reducing relapse rates or promoting Addressing non-adherence to prescribed antipsychotic recovery.15 This is in contrast to several naturalistic medication requires optimising pharmacotherapy studies that have demonstrated superiority for LAIs in by working with the young person to find the best reducing rehospitalisation rates.12 It has been suggested medication to treat their symptoms while minimising that people do not stay on LAIs for very long and that any side effects, this includes finding the lowest this may partially explain these results. Given their effective dose. This means that there must be close uncertain superiority, it is imperative that LAIs only communication and collaboration between the young be used with young people with early psychosis with person, the treating team and other significant supports their fully informed consent and where there is a good to understand the overall effect of the medication. clinical reason to do so.
Clinicians should also consider the young person's attitude and preferences regarding medication. Using Psychosocial interventions for non-adherence
a shared decision-making approach will help find the Psychological interventions targeting non-adherence best treatment for the young person and enhance to medications include: psychoeducation, cognitive– adherence to this. For more information, please see behavioural therapy (CBT) and motivational the clinical practice point Shared decision making. interviewing. Results of studies investigating the effectiveness of these interventions have been mixed, Long-acting injectable (LAIs) antipsychotic with some studies showing benefits of treatment on medications were developed as the ideal remedy for adherence, treatment acceptance and insight but poor adherence in psychotic disorders and proposed to others failing to do so. Multifaceted interventions offer the following benefits over oral medication:12 combining CBT, family interventions and community- • reduced family conflict around taking medication based approaches appear to be the most successful.16 • guaranteed delivery of medication• stable blood levels• clear signalling of non-adherence. Persistent positive symptoms
Beyond pharmaceutical agents, there is considerable The majority of work in incomplete recovery interest, research activity and emerging support for in psychosis has been around persistent positive the use of anti-inflammatory agents such as aspirin, psychotic symptoms because this was how the N-acetylcysteine (NAC) and omega-3 fatty acids concept was originally defined. There was also a lack (fish oil) to augment antipsychotic treatments.18,19 of recognition of the other symptoms of psychosis: functional outcomes and symptoms beyond positive psychotic symptoms.
Persistent positive psychotic symptoms are usually difficult for young people to cope with and can lead Pharmacological strategies
to feeling hopeless and disillusioned with treatment. A common response to incomplete remission of There may be the sense that things will never positive psychotic symptoms is to increase the dose improve, and powerful feelings of loss about both of antipsychotic medication or to introduce a second their future and former self. It is extremely important antipsychotic agent. However, evidence suggests that clinicians convey a sense of hope for recovery that an increase in antipsychotic dose above a and enhance coping strategies with every young moderate level is of little benefit, and currently, there person. Collaboratively exploring the young person's is no support for the efficacy of using combinations experience of psychosis in a non-judgmental manner of antipsychotic medications, thus antipsychotic engages them and reassures them that their problems monotherapy is strongly preferred.17 Instead, when are being taken seriously.
response to an antipsychotic medication is considered Psychological therapy for persisting positive psychotic suboptimal, it is recommended that the antipsychotic symptoms aims to foster the belief that it is possible medication be changed to one with a different receptor to manage and tolerate psychotic symptoms. Further, profile that may be better suited to the individual.
therapy can assist young people to gain awareness It is also recommended that clozapine be introduced of, and control over, things that trigger or exacerbate early in the course of incomplete recovery from symptoms. These may be internal or external events psychosis. Clozapine should be considered when that the young person can learn to exert an influence symptoms persist despite the sequential use of two over and, therefore, regain some power over their SGAs (at effective doses) for at least 6–8 weeks. Clozapine has been shown to be effective for both Psychological therapy for persistent positive psychotic positive and negative persistent symptoms of symptoms draws on psychoeducation, CBT principles psychosis. While many antipsychotic medications and the personal meaning of psychosis for the are thought to have ‘mind-dulling' effects linked individual. Components include: with negative symptoms, clozapine does not seem to have this effect. In addition, there is a low risk • developing a strong therapeutic relationship between of extrapyramidal side effects from clozapine. the therapist and the young person • developing a thorough understanding of the young person's history, illness onset, beliefs, aspirations, explanatory model of psychosis, and the impact of Although clozapine is considered the most efficacious of antipsychotic the psychotic illness available, its use is restricted to • providing psychoeducation about substance use, those with incomplete response or intolerance other comorbidities, psychotic symptoms and the of other antipsychotic medications due to the interactions between them risk of agranulocytosis. Agranulocytosis is • discussing the stress–vulnerability model an acute disease characterised by a dramatic of psychosis and normalising explanations decrease in the production of granulocytes of psychotic experiences (mature white blood cells) which means that • developing coping strategies (both cognitive and the body is susceptible to infections. This behavioural) for positive psychotic symptoms risk requires haematological monitoring on • working with beliefs about psychotic symptoms a weekly basis for the first 6 months, and to reduce their impact, and examining alternative monthly thereafter, to ensure that clozapine can continue to be used safely.
• using behavioural experiments to test explanations and develop better awareness and management of emotional arousal • working to understand the personal relevance and meaning of symptoms.
Persistent negative symptoms
Persistent negative symptoms have received less Careful and thorough psychological assessment attention than positive symptoms but are beginning of persistent negative symptoms will help clinicians to be the focus of research efforts. Hovington et al formulate the psychological factors underpinning the found that persistent negative symptoms are present in negative symptoms and provide treatment targets. about 27% of people with FEP.20 However, the authors Social withdrawal may be an understandable, self- noted that definitions of persistent negative symptoms protective reaction to overwhelming anxiety, blunting varied and included: severity, duration and aetiology, may be to avoid distress, and there may be strong thus hampering efforts to characterise this problem avoidance in the face of continuing positive psychotic and develop appropriate treatments. It is important to symptoms. Demoralisation and hopelessness can assess and treat persistent negative symptoms as they be due to fear, guilt, shame, and stigma can underlie are consistently associated with poor functioning 1 year extreme inactivity. All of these may manifest after beginning treatment.
as negative symptoms and be targeted within Pharmacological strategies
Although there are currently no widely accepted
The relationship and rapport between the clinician and medications for negative symptoms, considerable young person is paramount; therefore, session length, research is being undertaken and promising pace, location and frequency may need to be adapted suggestions are emerging. Amisulpride has the when severe negative symptoms are present to cope most evidence supporting its effectiveness as an with response latency and cognitive deficits.
antipsychotic monotherapy to treat negative Developing a formulation that incorporates a symptoms.21 The other strategy commonly employed hypothesis about the negative symptoms forms the is to add one of a number of promising agents as an basis of therapy, and provides the framework and adjunct to the currently used antipsychotic treatment. rationale for interventions. Clinicians should repeatedly Modest evidence supports the use of adjunctive communicate a sense of optimism and realistic hope antidepressant therapy, and there is limited but for recovery when working with young people around growing evidence for other agents (minocycline, incomplete recovery. modafinil, armodafinil and galantamine, see Arango, Garibaldi and Marder for review).21 There are also Elements that can be included in psychological work to non-pharmacological experimental treatments being address negative symptoms are presented in Box 1.
developed such as transcranial magnetic stimulation and direct current stimulation with some initial promising findings. The treatment of negative Box 1. Components in psychological
psychotic symptoms is a rapidly advancing field work to help manage negative
and stronger recommendations are likely to appear symptoms of psychosis
in the near future.
The following components can be included to Clinical experience at EPPIC in Melbourne suggests manage negative symptoms of psychosis: the following steps in approaching persistent negative • enhancing knowledge of self as distinct from symptoms in FEP. the psychotic illness (e.g. what else is the 1. Carefully assess whether persisting positive young person about?) symptoms are responsible for the appearance of • recognising personal strengths and identity negative symptoms. For example, ongoing paranoia may explain inactivity and reluctance to leave the • challenging self-defeating beliefs home. It is important to review whether there has • addressing stigma about mental illness been an initial response to treatment, or whether • gradually increasing exposure to anxiety positive symptoms are persisting.
provoking and challenging situations 2. Check for extrapyramidal side effects as these can • enhancing coping skills repertoire include slowing of mind and activity.
• building structure and pleasurable activities 3. Check for depression and treat if present using gradually into daily routine psychological or pharmacological therapy, or both.
• addressing comorbidities such as depression, 4. Consider treating depression even if not clearly post-traumatic stress disorder and substance present. Antidepressant medications have shown use problems.
efficacy for negative symptoms, and depression may be present but undetected.
5. Trial amisulpride as substitute or additional Persistent negative symptoms are the hardest to deal with because they usually involve low motivation and energy. You have to get to know the young person and their history really well. You need to talk to their family so that you can try to tap into things they have enjoyed … and get them doing those things again. You have to be really positive about them recovering but also let them know that it takes time.
Senior Clinician EPPIC, Orygen Youth Health Clinical Program TREAT encourages the early detection of incomplete Case management tasks that address quality and recovery through the clinical review system from meaningfulness of life are also important in combatting 3 months after service entry and the monitoring persistent psychotic symptoms (both positive and of those considered to be at risk. Presenting the negative). People need to have adequate housing and case to the panel at approximately 6 months of finances, and meaningful activities to be fully healthy, persistent symptoms facilitates a comprehensive and it is likely that this is also integral to achieving case and treatment review. This also supports the recovery from psychosis. Moreover, under the broader treating team to implement assertive and systematic, banner of psychosocial interventions, very recent guideline-concordant treatment. Recommendations evidence is emerging about the benefits of physical are made regarding ongoing treatment across the exercise for people with enduring psychosis. Positive biopsychosocial domains with the aim of accelerating results for an exercise intervention have been reported recovery. This may include expanding the treatment by Kahn and Sommer.22 team to include senior clinical specialists (e.g. family specialist or a senior clinical psychologist), which helps develop expertise in working with complex cases. Service-level response – the TREAT
The TREAT review ensures that all components example from EPPIC, Melbourne
of comprehensive treatment for FEP have been provided to young people and their families, and With the overarching goal of providing early problem-solves where this has not yet been achieved. intervention for psychosis to minimise disability There are opportunities for further TREAT reviews and maximise recovery, EPPIC has found it valuable so that progress can be monitored and clinicians to develop a specialised subprogram to address are supported in helping the young person.
incomplete recovery. Termed the Treatment Resistance Early Assessment Team (TREAT), this subprogram Experience has demonstrated that it is helpful to developed a framework for managing young people have all cases of persisting psychosis presented to who experienced prolonged recovery from FEP. the TREAT meeting regardless of the putative cause TREAT comprises a multidisciplinary team of senior of the ongoing psychosis. It is important that the clinicians with expertise and interest in the biological, review process is routine for the service, supported psychological and social aspects of persistent psychotic by management and experienced as supportive and collegial by the treating clinicians. I was seeing a young man, Jack, who did not seem to be getting better – he still Incomplete recovery is an important focus for early had auditory hallucinations and was not psychosis services because early treatment response leaving his house except for appointments. is predictor of outcome. Enduring psychosis increases I discussed his lack of progress with the risks of greater functional impairment and damage his doctor and we decided to ask the to social relationships. Incomplete recovery should be TREAT panel to review his case. We both detected as early as possible so that concerted efforts attended the meeting and presented our can be made to review and adjust treatment offered to avoid developing entrenched persistent psychosis. assessment, formulation and the treatment It is recommended that early psychosis services he had had since first coming to the service consider how to detect incomplete recovery in their 6 months ago. The TREAT panel noted young people and how best to support clinicians the over-protectiveness of Jack's mother to help their young people recover.
and suggested that she be offered some sessions with the family worker. It was also recommended that Jack's medication be changed as he did not seem to be responding to quetiapine. The doctor and I felt supported by the senior clinicians at TREAT, and Jack had improved (although he still had many problems) when we returned for another TREAT review after 3 months.
EPPIC, Orygen Youth Health Clinical Program talks about Jack and the TREAT experience References
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