Psychopharmacology: Schizophrenia

A. Hebephrenic schizophrenia

Classifying schizophrenia into subtypes is by no means simple in psychiatry. The term schizophrenia encompasses a heterogenous group of disorders, and as yet there has been no system of classification that has adequately been able to predict development of specific subtypes or reliable prognosis. That said, our current classification systems have divided schizophrenia into various types, and it does appear that, within limits, there is some utility to these categories. Hebephrenic schizophrenia (A) (sometimes referred to as ‘disorganized’ schizophrenia), is characterized by the predominance of thought disorder and affective symptoms. Social withdrawal is common. The affect is often fatuous and childlike. Delusions and hallucinations are often present, but are usually fragmented and are not the most striking feature. Negative symptoms tend to develop early and quickly, and for this reason this subtype is considered to have a poor prognosis. Catatonic schizophrenia (B) is characterized best by psychomotor disturbances, or catatonic behaviour. Catatonia is another complex concept which appears to have heterogenous aetiologies. In this subtype, there may be marked psychomotor retardation, with stupor, or florid over-activity. There are often unusual symptoms such as automatic obedience, in which people will follow a command without questioning, or the opposite (negativism). In severe cases, people may take on odd postures for long periods, or the limbs may be moved into positions and will remain there (waxy flexibility). Hallucinations and delusions may be present but again do not dominate the picture. For some unknown reason, catatonia appears to be much less common than in the middle part of the last century. Paranoid schizophrenia (C) is often thought of as the ‘classical’ subtype, and is dominated by delusions and hallucinations. Thought disorder is less common (although this is also contentious). Residual schizophrenia (D) refers to late-stage schizophrenia in which the syndrome of ‘positive’ symptoms (delusions, hallucinations, thought disorder) are replaced by predominately ‘negative’ symptoms (apathy, social withdrawal, avolition, blunting of affect, poverty of speech, selfneglect). Simple schizophrenia (E) is defined by ICD-10 as ‘the insidious development of oddities of conduct, inability to meet the demands of society, and decline in total performance’. There are usually no overt psychotic symptoms.

C. 0.4 per cent

Traditionally, the lifetime prevalence has always been quoted as 1
per cent, although most recent studies would suggest it is lower than this at around 0.4 per cent (with, obviously, some range around this). Regardless, this means the answer could only realistically be (C). Incidence rates are reported as lower (because of the chronic nature of the disease), usually between 0.17 to 0.54. Apart from a few exceptions, the prevalence of schizophrenia tends to be fairly standard across countries, with little overall sex differences.

E. The risk is about one in two

Schizophrenia is undoubtedly a disease with both genetic and environmental substrates. It is generally held that the genetic component accounts for approximately 50 per cent of susceptibility. Although there is some debate around this (more recent studies suggest heritability up to around 80 per cent, although there is large heterogeneity), (E) would be the only really feasible answer. There is undoubtedly an increased risk (B) of schizophrenia between identical twins, that is beyond that of sharing an ‘environment’. The risk of 1 in 100 (C) is approximately the risk in the general population (although see the question above; the prevalence may well have been overestimated in earlier studies). The risk of 1 in 10 (D) could be estimated to be the risk of developing schizophrenia if you have one first degree relative with the disease.

C. Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) (C) is a medical and psychiatric emergency. It often presents to accident and emergency or general practice so you must be familiar with recognizing it and the fundamentals of treatment – without treatment it has a mortality of up to 30 per cent. NMS occurs as a complication of antipsychotic medication use (and occasionally other psychotropics) and is thought to be the result of dopamine blockade in the hypothalamus (pyrexia) and nigrostriatal pathway (extrapyramidal symptoms such as tremor and rigidity). Peripheral blockade can cause changes in skeletal muscle contractility, which may exacerbate stiffness and cause muscle breakdown (with the consequent risk of rhabdomyolysis and renal failure). It must be treated as an emergency (although the syndrome is on a spectrum, and only mild or subclinical features may manifest) and appropriate referral is essential. As far as medical treatment is concerned, the offending antipsychotic must be immediately discontinued. Supportive treatment to ensure cardiovascular stability is the priority. Severe pyrexia may require other specialized cooling treatments. Some patients may actually require mechanical ventilation. It is unclear why some people develop NMS and others do not. It may be triggered on commencing treatment with antipsychotics, increasing dose or other environmental factors such as dehydration or exhaustion.

A. Aripiprazole

Aripiprazole (A) is a relatively newer antipsychotic. It appears to have less propensity to weight gain than other ‘second-generation’ antipsychotics (such as olanzapine) as well as a lower incidence of extrapyramidal side effects such as acute dystonias, although it does have its own side effect profile, notably nausea and insomnia. Out of the list, this would therefore be the best choice. Clozapine (B) is an extremely effective antipsychotic but is reserved for treatment-resistant schizophrenia because of its side effect profile. In this man, therefore, you would want to have trialled at least one (and probably two) other antipsychotics before moving to clozapine. Olanzapine (C) is one of the most commonly used secondgeneration antipsychotics. It is effective in treating positive symptoms, but has a marked propensity to cause weight gain and may worsen diabetic control. This would clearly be undesirable in this case. Oral haloperidol (D) would still be likely to cause acute dystonia – the patient is clearly very sensitive to these. Extrapyramidal side effects may be caused by either oral or intramuscular formulations. Sertraline (E) is an SSRI, a class of antidepressant, and would therefore not be an appropriate choice of drug in this case.

C. Section 3

While you would be unlikely to need in-depth knowledge of the MHA, many doctors (not just psychiatrists) may be called upon to use these Sections of the Act and it is a good idea to have some basic knowledge about the various ways that people are detained. Section 3 (C) is used to detain people for up to 6 months for treatment. It should not be used unless the person is known to services (and preferably to one of the professionals carrying out the assessment). According to the Department of Health’s code of practice, Section 3 should be used when: ‘the nature and current degree of the patient’s mental disorder, the essential elements of the treatment plan to be followed and the likelihood of the patient accepting treatment on a voluntary basis are already established’. This is therefore the most appropriate Section – an established and successful treatment plan has been in place previously. He will not come into hospital voluntarily and his pattern of relapse is similar to previous episodes. While a Section 2 is arguably less restrictive (being for a shorter period of time), he has also had a recent previous admission under Section. Both Sections require two medical recommendations and an application by an Approved Mental Health Professional (AMHP).

C. Lorazepam 2mg intramuscular

Rapid tranquilization should only be used when non-pharmacological methods have failed and the risks to the patient or those around them are sufficiently high. Do not use rapid tranquilization without senior advice. This man is obviously unwilling to take oral medication, which makes (B) an inappropriate choice. Haloperidol decanoate (A) is a depot medication and would therefore not have an immediate effect, making this an inappropriate choice also. While lorazepam may be given as a slow intravenous injection (D), it is more likely to cause difficulties such as respiratory depression using this route, and on a mental health unit there are unlikely to be staff or equipment capable of monitoring this. Propofol (E) is used to induce anaesthesia so clearly would not be an appropriate medication. Lorazepam intramuscularly is a commonly used drug for rapid tranquilization, and this would be a reasonable starting dose. It is often combined with intramuscular haloperidol (not the depot formulation). Patients prescribed rapid tranquilization should be carefully monitored by nursing and medical staff to ensure there is no evidence of respiratory depression or other side effects. Before giving parenteral benzodiazepines, ensure the ward has a supply of flumazenil (a benzodiazepine antagonist).

E. Low neutrophil count

Clozapine has been known to cause neutropenia (E) or even agranulocytosis. This can lead to infection and sepsis, which would fit with the clinical picture here. This requires urgent treatment and the clozapine must be immediately stopped. This could also be neuroleptic malignant syndrome from the clinical picture, but the haematology does not particularly fit – you would expect to see raised leukocytes. There have been reports of eosinophilia (A) with the use of clozapine, but the exact mechanisms of this are complex and unclear. It is likely to be related to the side effects of myocarditis or colitis that can sometimes be seen with the use of clozapine. Either way, the clinical picture does not quite fit with this. Thrombocytosis (B) has been reported with clozapine but this would be unlikely to lead to this clinical picture. Similarly, anaemia (C) has occasionally been seen, but the clinical picture is closer to one of sepsis rather than anaemia. A low lymphocyte count (D) may be present as part of an overall decrease in all white blood cells with clozapine, but would be unlikely as an isolated abnormality

A. Gradual decrease in depot medication

This symptom is tardive dyskinesia (TD), which generally occurs in those taking antipsychotics (particularly older depot antipsychotics) over many years. It is distressing as well as socially, if not physically, disabling. There are numerous theories about why it occurs, although none has been universally proven. The best course of action in this case would be to try a gradual decrease in the depot medication (A), particularly as the man has been well for so long. This should be done with extreme caution and under regular medical supervision. Approximately 50 per cent of cases of TD improve. Decreasing the depot may cause an initial worsening of symptoms which should be explained to patients.

E. Rapid onset of symptoms

Curiously, having a rapid onset of symptoms (E) appears to confer a positive prognosis in schizophrenia. All of the other options are associated with a poor prognosis – being male (B), having no mood
symptoms in the clinical picture (A), being younger at onset (C), and showing an initial poor response to treatment (D). Other poor prognostic markers include lack of social networks, being single, poor pre-morbid educational attainment, having predominantly negative symptoms and having a long duration of illness before treatment.

B. de Clérambault’s syndrome

This is a classic example of de Clérambault’s syndrome (B), also sometimes known as ‘erotomania’, in which the sufferer, usually a single woman, becomes delusionally convinced that someone of ‘exalted’ (in current society usually famous) status has become infatuated with them. The delusion is often meticulously constructed, as the sufferer can explain why the object of their affection cannot reveal their feelings, although obviously the explanations are often outlandish or bizarre. The syndrome can cause considerable problems for the targeted person. Note this is not the same as stalking, although some stalkers will suffer with this syndrome. It is often, but not always, part of the picture of a schizophrenic illness

C. Hyperprolactinaemia

C This is likely to represent hyperprolactinaemia (C), which is a relatively common side effect of many antipsychotics, and by no means limited to the older antipsychotics. It is caused by dopamine blockade of the tuberoinfundibular pathway which regulates prolactin secretion. Symptoms of raised prolactin include gynaecomastia and sexual dysfunction. It is a significant side effect that must be treated seriously. Ignoring it may lead to poor compliance and, in the long term, sustained prolactin levels may lead to osteoporosis. Alpha-blockade (A) from antipsychotic use may lead to sexual dysfunction but would not explain the gynaecomastia. Drug-induced hepatitis (B) would be an unusual finding with haloperidol but it has been reported. Also, these symptoms would be unlikely to be the ones causing hepatitis to present. New-onset diabetes (D) is unlikely to cause sexual dysfunction at early stages, and gynaecomastia would only develop in the context of chronic kidney disease. This is therefore an unlikely option, especially as haloperidol is far less likely than some of the newer antipsychotics to cause problems with blood sugar.

B. Grandiose delusions

This question refers to the ICD-10 diagnosis of schizophrenia, and should not be mistaken with first-rank symptoms, which is a common mistake made. Grandiose delusions (B) are more commonly associated with mania, and as such are not specified in ICD-10 for the diagnosis of schizophrenia. Some delusions in schizophrenia, however, can sometimes appear to have a grandiose characteristic, such as believing that the CIA are targeting the individual using brain waves – this would more accurately be described as a ‘persecutory delusion’. Formal thought disorder (A), including neologisms (new words being used), metonyms (existing words used in unusual ways) and tangential thinking (unusual connections made between thoughts) are relatively common in schizophrenia, particularly in the acute stages of the illness. Running commentary (C) is when one or more hallucinatory voices comment continuously on what the patient is doing, for example, ‘he’s walking to the shop now, turning left, over the road, why does he look so stupid when he does that?’. It is strongly suggestive of schizophrenia. For a diagnosis according to ICD-10, the symptoms must have been present for most of the time for a period of at least 1 month, or at some time on most days (D). Thought broadcasting (E), in which the sufferer believes that their thoughts are being transmitted so others can hear them, is also relatively common in schizophrenia. Similar symptoms include thought insertion and thought withdrawal and are sometimes collectively known as symptoms of thought alienation.

D. Schizoaffective disorder

This appears to be a schizoaffective disorder (D) of the manic type. The nature of these disorders is a topic of some debate, but according to ICD-10 they occur when both schizophrenic (in this case delusions of passivity in terms of being controlled by the Nazi party as well as auditory hallucinations) coexist with a diagnosable affective disorder (in this case clear manic symptoms). Both must be present within the same episode for the diagnosis to be made. This is not a classic presentation of hebephrenic schizophrenia (A) in which delusions and hallucinations are fleeting and not predominant, but a shallow and inappropriate affect tends to dominate the clinical picture. Disorganized behaviour and speech are also more prominent. An induced delusional disorder (B) is another term for a ‘folie à deux’ in which a delusion appears to be ‘passed on’ from someone with a psychotic belief to someone close to them, usually in an isolated relationship from the rest of the world. An example would be an isolated couple in which the wife wrongly believes she is pregnant and this belief is then shared by the husband.

D. Renal failure

There is almost no evidence for antipsychotics causing renal failure (D), although of course if they precipitate neuroleptic malignant syndrome then this may lead to renal failure through rhabdomyolysis. Also, most antipsychotics are metabolized hepatically, so dose adjustment even in renal disease is usually not indicated (although there are exceptions such as amisulpride). Akathisia (A), or restlessness, is certainly a recognized and common side effect of antipsychotics, particularly those with a propensity for extrapyramidal side effects. Convulsions (B) can occur with antipsychotic use as they tend to lower the seizure threshold. Clozapine significantly reduces seizure threshold, and seizures are a very real possibility for those taking this drug. Hypotension (C) occurs in antipsychotics with adrenergic blockade properties and is usually dose related. These medications should be titrated initially to prevent sudden hypotension and collapse, particularly in the elderly. Tachycardia (E) is also a recognized side effect of antipsychotics. It may be a portent of other more serious cardiac abnormalities with antipsychotic use, such as cardiac arryhythmias and prolonged QT interval, which may lead to sudden cardiac death.