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Choosing the right therapy

Discussion

Schizophrenia is a complex, life-altering mental illness which not only impacts the individual affected but also their family, wider social circle and society as a whole. Schizophrenia can prevent affected individuals achieving their personal, social and professional potential, with palpable costs to both the individual and society. Individuals with schizophrenia are over-represented in our prisons.

Ireland’s experience adheres to Penrose’s Law, a phenomenon noted worldwide in which the prison population increases as the number of psychiatric inpatients decreases. The Irish psychiatric inpatient population decreased by 81.5 per cent between 1963 and 2003, while the prison population increased five-fold.

Given the myriad of negative consequences schizophrenia entails for both the individual, their family, social circle and society as a whole, it is crucial we provide the best treatment possible. Arguably the greatest barrier to successful treatment of schizophrenia is non-compliance with prescribed antipsychotic medication.

Compliance can be defined as: ‘the extent to which the patient’s behaviour, in terms of taking medications, following diets, executing lifestyle changes, coincide with the clinical prescription’. Even the best medication in the world is useless when it is not taken but merely sits uncollected in a pharmacy or, worse yet, is collected but untaken in a drawer in the patient’s home.

Non-compliance rates in schizophrenia vary but rates of over 50 per cent are commonly observed, with one thorough systematic analysis demonstrating that less than 50 per cent of patients prescribed antipsychotic medication remained compliant after 13 months.

While it is seductive to imagine that we each possess such finely-honed clinical and deductive skills that we are, in a Sherlock Holmesian manner, able to ‘sniff-out’ any patient who is non-compliant and persuade them of the benefits of adhering to oral antipsychotic treatment, the reality is quite different.

In a recent study comparing the rate at which patients collected prescribed oral antipsychotic medications from their pharmacies with the rate of compliance estimated by their treating doctors, 94 per cent of patients with low-to-moderate compliance were incorrectly rated by their treating doctors as being highly adherent. Cochrane reviews and previous systematic analyses have shown questionable benefits for concordance therapy and other forms of patient education in isolation in those with schizophrenia.

Variables which most closely correlate with improved compliance appear to be patient insight and a good patient-reported therapeutic relationship with their treating doctor, but these are often difficult to achieve clinically.

Indications for LAIAs

LAIA medications are, according to the Maudsley Guidelines, not to be used when poor compliance is related to poor tolerability. They are to be used when poor compliance is driven by poor insight and negative patient attitudes towards antipsychotic medication.

If poor compliance is driven by poor tolerability, then it is recommended that a discussion of side-effects be arranged with the patient and the issue of reducing the dose or switching to another oral antipsychotic discussed with them.

Factors associated with non-compliance

The factors most commonly associated with non-compliance are:

  • Poor patient insight into their illness

Patients with poor insight into their mental health difficulties are likely to have poor compliance with prescribed treatment. Would you willingly take medication which you either felt did not benefit you or was for an illness you did not believe you suffered from? I certainly would not, and so empathise with and understand those patients for whom lack of insight drives non-compliance.

  • Previous non-compliance with prescribed medication

While financial institutions and stockbrokers remind us that past performance is no guarantee of future performance, in the field of psychiatry previous non-compliance with prescribed medications is powerfully correlated with future non-compliance. Whenever non-compliance has occurred in the past, it is essential to discuss with the patient the reasons for this non-compliance and, where possible, address these reasons both with the patient and in your management plan.

  • Patient-reported poor therapeutic relationship with their treating doctor

A good therapeutic relationship between patient and treating doctor is an essential component of much of the work we do in medicine and, particularly, psychiatry. It is impossible to have great rapport with every patient but by emphasising one’s openness and willingness to consider different viewpoints, and the right of both yourself and the patient to disagree openly and honestly with each other, it is more likely to foster a good therapeutic relationship. It is important to remember that a good therapeutic relationship does not require the patient to follow all of your advice. Sometimes a good therapeutic relationship requires agreeing to disagree, advising a patient of the likely outcome of a decision and truthfully hoping they beat the odds you have just outlined.

  • Negative attitudes or subjective responses to antipsychotic medication

Many patients will come to the consult with strongly-held, pre-existing negative beliefs towards antipsychotic medication. There is often nothing more difficult than countering the belief that a person wishes to hold, often in spite of a great weight of evidence to the contrary. Often, the most that is possible is to state what the evidence shows, provide the best clinical advice possible given the evidence and then agree to disagree in order to preserve the therapeutic relationship. Rome wasn’t built in a day and often the path to insight and compliance takes time — sometimes months and years of it.

  • Concomitant substance abuse

All of above becomes exponentially more difficult in the presence of concomitant substance abuse. If a schizophrenic patient is abusing drugs, one has to tackle the twin tasks of convincing them of the negative effects of continued substance abuse while advocating for compliance with antipsychotic medication, occupational therapy and other treatment modalities. It may be hard enough to successfully communicate even one of those messages. Communicating both at the same time is exceedingly difficult.

Often, progress in such situations can appear to be non-existent until such time as the consistent repetition of this evidence-based message eventually meets a patient whose viewpoint has changed and is ready to engage with the advice being given.

Benefits and efficacy of LAIAs

LAIAs have been shown to be more effective in reducing the risk of relapse than oral antipsychotics in schizophrenic patients. This is enhanced by the presence of insight and a good therapeutic relationship with the treating doctor but is not dependent on it.

Naturalistic studies show a larger benefit for LAIA medications over oral antipsychotic medications compared to more laboratory-based studies. This may be because compliance with oral antipsychotic medication is higher in more laboratory-based studies than occurs naturally in schizophrenic patients living in the community.

A recent Canadian study of 1,992 outpatients demonstrated that following the initiation of LAIA treatment, there was an approximately 30 per cent increase in compliance with treatment, an approximately 50 per cent reduction in the number of days hospitalised and more than 40 per cent reduction in costs to the health service. This reduction in costs was largely driven by the decrease in number and length of hospitalisations.

In addition to these concrete benefits, there are a number of less obvious benefits which may accrue to patients on LAIA medication. As most LAIAs are given either fortnightly or monthly, there are often increased levels of interaction with members of the multidisciplinary mental health team, particularly the community mental health nurses who usually administer the injections. These experienced staff can use these frequent interactions to build therapeutic rapport and also to assess the mental state of the patients when they attend, providing a pathway for additional interventions and early recognition of relapse.

Non-adherence to treatment is also much easier to recognise for patients on LAIAs. A patient on oral antipsychotics may still pick up their medication from the pharmacy every week and deny non-compliance upon direct questioning. Often, only collateral history from family members, if living at home, or relapse uncovers non-compliance with oral medications. With an LAIA, monitoring is much easier; either the patient presented to clinic and received the injection or they did not. Simple, clear and actionable.

Tolerability of LAIAs

All medications, including LAIAs, have side-effects. These side-effects can be one of the main drivers of non-compliance and can be much more easily addressed than a lack of insight or negative beliefs regarding antipsychotic medications.

When addressing the side-effects of LAIAs, the first priority is to be open about the reality of side-effects and to attempt to form a therapeutic rapport with the patient aimed at finding the best balance between treatment outcome and side-effects.

This demonstrated openness to discussion may encourage patients who would otherwise become non-compliant choosing, instead, to discuss the side-effects with you in order to seek solutions other than discontinuation of the medication.

Apart from demonstrating an openness to discussing and treating side-effects, there are several steps that can be taken to concretely reduce the risk of side-effects occurring. These include:

  • Giving a test dose initially

Since LAIAs are, by definition, long acting, any adverse effects that occur are likely to persevere. For first-generation LAIAs, a test dose comprising a small amount of the medication should be given, both to test the patient’s sensitivity to extra-pyramidal side-effects and any sensitivity to the oil contained in the depot. For second-generation antipsychotics, the likelihood of extra-pyramidal side-effects is much reduced but the possibility of sensitivity to the oil contained in the depot remains, so while a test dose is not as essential, it can still be of use.

  • Begin with the lowest therapeutic dose possible

Since low doses are likely to be better tolerated by patients, and side-effects are one of the main reasons schizophrenic patients fail to adhere to their antipsychotic therapy, the lowest dose of an LAIA that effectively treats the patient’s illness should always be used.

  • Adjust the dose only after an adequate period of assessment

Attainment of peak plasma levels, steady-state plasma levels and therapeutic effect are all delayed with depot injection. A period of at least one-to-two months should be allowed before any conclusions are drawn regarding suitable doses. Prior to this time, decisions are likely to be made before the patient’s steady state plasma level is reached and will almost certainly need to be revisited once the steady state plasma level is attained. One significant exception to this is if significant side-effects occur. If serious side-effects occur, then they are only likely to worsen as the plasma level increases and the antipsychotic dose or the possibility of switching to another antipsychotic entirely should be examined.

Conclusion

LAIA medications are not a panacea but they have a role in those patients who are non-compliant with oral antipsychotics for reasons other than tolerability. In this group of patients, LAIAs can improve compliance with treatment, reduce the number of hospitalisations and the number of patient days in hospital, as well as reducing the cost of treatment to society.

With the health budget under pressure, alongside a reduction in inpatient psychiatric beds as part of the drive to care for patients in the community, it is likely that LAIA medications will continue to be a mainstay of treatment for a significant portion of schizophrenic patients.

References available on request

Case report

A 24-year-old male with a five-year history of schizophrenia was admitted to hospital following a relapse of his psychotic symptoms after self-cessation of his medications. He had been admitted on three occasions over the previous two years. Each admission was preceded by the self-cessation of his oral antipsychotic medication after he felt well.

After each relapse he had responded well to oral antipsychotics, had engaged well with occupational therapy and had appeared to comply with his treatment by attending outpatients and collecting his medications from the pharmacy. However, it transpired that he had been flushing the medications down the toilet and filling his prescriptions as a means of camouflaging his non-compliance.

On this admission, an oral antipsychotic with a long-acting injectable version was commenced. Once he began to improve, the option of a long-acting injectable antipsychotic (LAIA) was discussed with him and, with his consent, commenced. Four weeks later, as he continued to improve he was discharged with intensive follow-up in the outpatient clinic and by the team’s community mental health nurse.

Since discharge, he has formed a good therapeutic rapport with the community mental health nurse and been compliant with all outpatient clinic and depot appointments. He is currently engaging with occupational therapy and is awaiting placement on a rehabilitative education course with a view to re-skilling and obtaining full-time employment.

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