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Independents' Day

Need to know - schizophrenia

Psychiatrist Dr Mark Salter answers GP Dr Mandy Fry’s questions on using depots, changes to the benefit system, the effects of cannabis and emergency sedation

Psychiatrist Dr Mark Salter answers GP Dr Mandy Fry's questions on using depots, changes to the benefit system, the effects of cannabis and emergency sedation

1 NICE appears to recommend the newer atypical antipsychotics for people newly diagnosed with schizophrenia. Are any of these available in depot preparations or do you always have to use the older agents for patients in whom compliance is an issue?

41208023 Most of the ‘old' depots are oily esters that are well suited to slow release from intramuscular tissue, but the complex structure of the newer molecules makes them hard to esterify.

The only atypical antipsychotic available in a long-acting depot preparation is risperidone, in the form of Risperdal Consta. Although this is a reliable drug at a dose ranging between 25mg and 50mg, it has some snags. A larger needle is required for injection as the active component is not a fatty ester, but instead is embedded in a polymer matrix that dissolves slowly in the muscle bed.

This takes time to reach useful tissue levels, so will need covering with an oral drug. It will also need replenishing after a maximum period of a fortnight, unlike typical depots, where the dosage can be stretched to weeks and even months.

Despite these drawbacks, risperidone does have the advantages of the newer drugs, especially in terms of the better extrapyramidal side-effect (EPSE) profile.

2.As with many mental illnesses, schizophrenia often seems to follow a relapsing and remitting course. I can anticipate that this may cause problems with the Government's plans in relation to changing incapacity benefit to an employment support allowance. How would you advise us to support patients who may be caught in this transition?

The occupational outcome of schizophrenic illness is very diverse. Individuals with good premorbid adjustment and who receive effective early intervention can expect to return to a good level of function, and so will ultimately require less financial support. Others – often from deprived urban settings – will have a more chronic outcome. Such diversity will not suit the one-size-fits-all approach that is typical of welfare and benefits policy.

The solution lies in careful individual assessment of functioning over time.

Given the influence of stigma upon the employment prospects after any psychotic illness – and the fact that most patients with a psychotic illness who remain in touch with their GP or secondary care are likely to have a degree of chronic disability – it seems sensible to err on the side of caution. Try to secure them every penny on offer, while never abandoning the hope of eventual return to gainful employment.

3 Are people with schizophrenia at risk of any particular associated physical health problems, apart from those that may result from a degree of self-neglect?

Yes. Patients with schizophrenia are recognised to be at increased risk of diabetes, cardiovascular disease and pneumonia. Overall morbidity for populations with schizophrenia is much higher than average, with a shortened life expectancy of about 10 years.

Lifestyle seems to be only one of several explanations. A reluctance to seek help and the tendency of many health professionals to overlook reported symptoms in psychiatric cases probably play an important part. These individuals may also react differently to bodily signals that other individuals would recognise as problems.

Many such patients smoke heavily. Alcohol and drug misuse, as well as an indolent lifestyle, are common. In addition, antipsychotic medication is associated with weight gain and disruption of glucose metabolism, leading to many problems associated with the ‘metabolic syndrome'.

4 How do you decide which antipsychotic therapy to use in a given individual? Are any of them particularly good at addressing the more negative symptoms of schizophrenia? What role does combination therapy play?

Despite many claims, finding the right drug is still largely a question of trial and error, but some useful rules apply. The newer atypicals really do seem to be cleaner in terms of EPSEs, but bring problems of their own, especially in terms of weight gain, and occasionally gynaecomastia and galactorrhoea.

Risperidone tends to ‘go typical' in terms of EPSEs above 8mg per day and olanzepine similarly above 20mg. Quetiapine, on the other hand, seems to have a flatter dose-EPSE graph across its dose range, but is more sedating when first given and usually needs to be taken to the higher end of the range to be fully effective. One unusual drug is aripiprazole, which has a mixed agonist-antagonistic effect on cerebral dopamine and seems to have activating properties. Amisulpride seems relatively non-sedating.

Another unusual drug is clozapine, which in spite of well-known toxicity problems, is often effective in treating resistant cases. The reasons for this are unclear.

Whether any of these drugs are truly effective on so-called negative symptoms remains unanswered, in part because many negative symptoms are in fact positive symptoms in disguise. Mute, undermotivated or socially withdrawn patients, while seeming ‘negative' may in fact be displaying depression, iatrogenic parkinsonism or withdrawal from the world – or simply be so psychotic as to be too lost inside their mental state to respond to the outside world.

5 It seems that many individuals on depot medication seem to get this from the local mental health services and so there is often a delay in GPs receiving information regarding changes in dose or even preparation. Although this is clearly not ideal, are there any particularly common drug interactions that we should take care to avoid when treating these individuals in primary care?

Most of the depot medications are safe and rarely induce enzymes or otherwise interact in ways that prove problematic to the use of other drug treatments.

Depot antipsychotic drugs, like the stable patients who receive them, are easily overlooked and may go for years without anyone considering reducing the dose.

Depots are indeed still widely administered from local mental health services. This may be related to the stigmatising assumption that psychotic illness and its treatment is somehow ‘different' and will always require specialist care. But many other depots are given in primary care without any difficulty.

Whatever the reasons, poor communication of dose changes between primary and secondary care is simply bad practice, and it is the responsibility of both sides to address this.

PCTs across the UK are beginning to recognise this problem and encouraging group practices to develop in-house enhanced mental health services that allow them to take back depot patients with little difficulty, freeing secondary services to attend to more pressing psychiatric morbidity. If this is not yet routine in your practice, contact your local catchment area psychiatrist.

6 People with schizophrenia often seem to be obese, perhaps as a consequence of their depot medication. How can we best support these individuals to lose weight? What role do drugs like orlistat play?

Obesity is common in patients with schizophrenia, particularly women. Weight gain is significantly associated with antipsychotic drug treatment. Olanzapine and clozapine seem particularly troublesome. Many factors beyond iatrogenesis, however, contribute to obesity. Poor dietary habits, impecunity, unreliable access to cooking facilities, an indolent lifestyle and a preference for high-calorie ‘comfort' foods may all play a part, as does poor knowledge of a healthy diet.

The best solutions are non-pharmacological. Body mass, age, gender and past response to treatment should all be taken into account when starting, switching or changing the dose of any antipsychotic drug.

Nutritional assessments and weight-loss interventions may also be useful, although some dietetic departments exclude ‘psychiatric patients' from their services.

Exercise programmes can be effective for patients with schizophrenia and can have benefits that go well beyond simple weight reduction.

Physical fitness is easily overlooked in many people with mental illness, possibly because they require higher levels of persuasion to engage effectively.

But patience, persistent encouragement and realistic goal-setting, along with the use of diaries and reward schedules, in the context of a trusting relationship with the patient can prove effective. This can be incorporated into a patient's care plan. Weight-controlling drugs probably have little role to play in this situation.

7 What is the current thinking behind cannabis and schizophrenia? If a cannabis user develops a psychotic illness how can you distinguish between a drug-induced psychosis and schizophrenia?

Regular cannabis use is a modest but significant risk factor for schizophrenic illness in vulnerable individuals. Because the issue of ‘drugs' is so politicised, research in this field warrants careful scrutiny. We must distinguish between absolute risk and relative risk; a doubling of risk from 2% to 4% still leaves 96% of people unaffected. Many young people use cannabis, yet only a small proportion of them go on to develop schizophrenia.

Pure ‘dope smoking' subjects are rare, as drug users often lead lifestyles that

carry other potent risks for mental illness. Furthermore, cannabis is not a homogeneous entity. Different preparations may vary by as much as 10 times in terms of their active ingredient.

Against this, we must consider the controversial and clinically important observation that some people with schizophrenia actually find the relaxant properties of low-dose cannabis helpful.

Symptomatically, there is little to distinguish drug-induced psychosis from ‘true' schizophrenia and it is probably an unhelpful distinction. Where cannabis plays a major causative role, and all other things being equal, the acute phase of the illness often subsides over weeks rather than months, typically with a better chance of return to a reasonable level of mental function.

8 Very occasionally as GPs we need to be able to sedate individuals who are in acute psychiatric distress. What would you advocate as being the safest and most effective drug to carry in our emergency bag for these rare occasions?

Thankfully, this will happen only rarely, but in such situations the rules are the same as for acute inpatient settings, where the most often used combination is intramuscular lorazepam and intramuscular haloperidol. Of the two, it is safest to use the benzodiazepine in the first instance and, even then, it is important to make sure that all feasible non-drug efforts at de-escalation have been tried, or at least considered.

Lorazepam is well absorbed and should be used at a dose of 1-2mg, erring towards the latter for a male of medium build, and the dose range for haloperidol similarly is between 5mg and 10mg. Allow 15 to 20 minutes for full effect. Once administered, the patient must never be left unattended. Careful attention must be paid to cardiovascular and respiratory status, especially where restraint has been used, or where alcohol or other sedatives may have coloured the clinical picture.

9. What proportion of people with schizophrenia go on to develop tardive dyskinesia as a result of their medication? How can we minimise the risk? What is the best approach to take once symptoms have developed?

Tardive dyskinesia (TD) is one of the nastier complications of long-term treatment with neuroleptic drugs. Fortunately, for most patients, the abnormal movements are not progressive. It used to be thought that the risk of developing TD was simply proportional to the area under the time-dose curve, but we now know that things are more complicated.

Age and female gender are also significant risk factors, and in such high-risk groups the incidence of TD may reach 40%.

Another possibility is that TD may even be part of the illness process itself. There is some historical evidence for this: high levels of TD-like syndromes were reported among the inmates of Victorian asylums, long before chlorpromazine was invented.

There is no definitive treatment for TD, but reducing or stopping medication usually leads to improvement, especially in younger patients. Discontinuation must always be balanced against the risk of relapse.

Oddly, TD may show transient improvement with increased dosage and several case reports have shown significant improvement on switching to clozapine. It is too early to say whether the atypical drugs are associated with a lower incidence of the condition.

10 Should patients on the older antipsychotics routinely be prescribed drugs such as procyclidine to help with side-effects or should we wait until they actually develop side-effects? What are the best drugs to use, and at what dose?

No. Not everyone starting the older drugs displays these symptoms, especially if they are used at a lower dose, and although this runs the risk of some distress in the short term, it avoids the harm of unnecessary polypharmacy in the longer term. A better approach is to remain vigilant to the occurrence of EPSEs every time you see the patient and consider modification of the primary drug.

Anticholinergic drugs, such as procyclidine and orphenadrine, may cause problems of their own with subtle cognitive impairment and may even raise the risk of TD over the longer term. In addition, these drugs can easily be misused, as they can have a mild, pleasant stimulant effect, especially when taken in doses just beyond the top of the range reported in the BNF, or when combined with caffeine. Always consider this when patients make regular requests for repeat prescriptions of these drugs and if you have concerns, discuss the case with your local psychiatric team.

Dr Mark Salter is consultant in adult general psychiatry in Hackney, East London, and a member of the public education committee of the Royal College of Psychiatrists

Competing interests: none declared

PET scan of brain of patient with schizophrenia (right) showing lower activity in frontal lobes compared with normal activity (yellow) in unaffected brain (left) PET scan of brain of patient with schizophrenia (right) What I will do now What I will do now

Dr Mandy Fry responds to the answers to her questions
• I will carry out an audit to ensure that we have accurate doses for all of our patients on depot preparations
• I'll also see whether there are any individuals whose injections we could take back from mental health services
• I will keep screening for physical heath problems and encourage patients to look after their physical health needs
• I will consider alternative explanations, such as increasing psychotic symptoms, in socially withdrawn individuals
• I will continue to encourage patients to participate in exercise programmes and liaise with the local leisure centre
• I will continue to carry lorazepam in my bag for emergencies

Dr Mandy Fry is a GP in Cirencester, Gloucestershire, and senior primary care lecturer at Oxford Brookes University

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