Psychoses and related disorders Flashcards
positive symptoms
hallucinations
delusions
negative symptoms
emotional apathy and withdrawal
prodromal
characterised by some deterioration in personal functioning and emergence of negative symptoms.
acute phase
marked by positive symptoms which may resolve or reduce following treatment, but in some cases negative symptoms can remain and interfere with daily functioning.
antiphsychotics are more effective at treating which type of symptoms
positive
first line treatment for patients with schizophrenia
An oral antipsychotic drug in combination with psychological therapy should be offered to patients with schizophrenia.
choice of drug depends on
factors such as the potential to cause extrapyramidal symptoms (including akathisia),
cardiovascular adverse effects,
metabolic adverse effects (including weight gain and diabetes),
hormonal adverse effects (including increase in prolactin concentration), and
patient and carer preference.
how long must a drug to be used to determine effectiveness
titrate low and slow
Patients should receive an antipsychotic drug at an optimum dose for 4–6 weeks before it is deemed ineffective.
can more than one antipsychotic be used at once
Prescribing more than one antipsychotic drug at a time should be avoided except in exceptional circumstances (e.g. clozapine augmentation or when changing medication during titration) because of the increased risk of adverse effects such as extrapyramidal symptoms, QT-interval prolongation, and sudden cardiac death. It is important to record the reasons for continuing, changing, and stopping treatment, and the effects of such changes, including side-effects experienced.
when should clozapine be offered
Clozapine should be offered if schizophrenia is not controlled despite the sequential use of at least 2 different antipsychotic drugs (one of which should be a second-generation antipsychotic drug), each for an adequate duration. If symptoms do not respond adequately to an optimised dose of clozapine, consider other causes of non-response (e.g. adherence to therapy, concurrent use of other drugs), review diagnosis, and check plasma-clozapine concentration before adding a second antipsychotic drug to augment clozapine; allow 8–10 weeks’ treatment to assess response. Patients must be registered with a clozapine patient monitoring service.
first generation antipsychotics
how do they work and examples
The first-generation antipsychotic drugs (also known as typical or conventional) act predominantly by blocking dopamine D2 receptors in the brain. They are more likely to cause a range of side-effects, particularly acute extrapyramidal symptoms and hyperprolactinaemia.
First-generation antipsychotics include the phenothiazine derivatives (chlorpromazine hydrochloride, fluphenazine decanoate, levomepromazine, pericyazine, prochlorperazine, promazine hydrochloride, and trifluoperazine), the butyrophenones (benperidol and haloperidol), the thioxanthenes (flupentixol and zuclopenthixol), the diphenylbutylpiperidines (pimozide) and the substituted benzamides (sulpiride).
2nd generation antipsychotics
how do they work and examples
The second-generation antipsychotic drugs (also referred to as atypical) act on a range of receptors in comparison to first-generation antipsychotic drugs and are generally associated with a lower risk for acute extrapyramidal symptoms and tardive dyskinesia; the extent varies between individual drugs. However, second-generation antipsychotic drugs are associated with several other important adverse effects, such as weight gain and glucose intolerance.
Second-generation antipsychotics include amisulpride, aripiprazole, asenapine, cariprazine, clozapine, lurasidone hydrochloride, olanzapine, paliperidone, quetiapine, and risperidone.
what is a high dose antipsychotic
total daily dose of a single antipsychotic drug which exceeds the maximum licensed dose with respect to the age of the patient and the indication being treated, and a total daily dose of two or more antipsychotic drugs which exceeds the maximum licensed dose using the percentage method.
are high dose antiphsychotics more effective
There is no robust evidence that high doses of antipsychotic drug treatment is any more effective than standard doses for the treatment of schizophrenia. The majority of adverse effects associated with antipsychotic treatment are dose-related and there is clear evidence for a greater side-effect burden with high-dose antipsychotic drug use. Antipsychotic polypharmacy and ‘when required’ antipsychotic drug treatment are strongly associated with high‐dose prescribing.
antipsychotic use in the elderly
Antipsychotic drugs should not be used in elderly patients with dementia, unless they are at risk of harming themselves or others, or experiencing agitation, hallucinations or delusions that are causing them severe distress.
The lowest effective dose should be used for the shortest period of time.
Treatment should be reviewed regularly; at least every 6 weeks (earlier for in-patients).
Extrapyramidal symptoms
Extrapyramidal symptoms consist of:
parkinsonian symptoms (including bradykinesia, tremor), which may occur more commonly in elderly females or those with pre-existing neurological damage such as stroke, and may appear gradually; dystonia (uncontrolled muscle spasm in any part of the body), which occurs more commonly in young males; acute dystonia can appear within hours of starting antipsychotics; akathisia (restlessness), which characteristically occurs within hours to weeks of starting antipsychotic treatment or on dose increase and may be mistaken for psychotic agitation; tardive dyskinesia (abnormal involuntary movements of lips, tongue, face, and jaw), which can develop on long-term or high-dose therapy, or even after discontinuation; in some patients it can be irreversible.
management of tardive dyskinesia
Tardive dyskinesia is the most serious manifestation of late-onset extrapyramidal symptoms for which there is no satisfactory treatment; it occurs more commonly in elderly females. Antipsychotic treatment should be carefully and regularly reviewed; any changes to dose or drug should be made gradually, over weeks or months, to minimise the risk of withdrawal tardive dyskinesia. However, some manufacturers suggest that drug withdrawal at the earliest signs of tardive dyskinesia (fine vermicular movements of the tongue) may halt its full development.
Hyperprolactinaemia
Most antipsychotic drugs, both first- and second-generation, increase prolactin concentration to some extent because dopamine inhibits prolactin release.
Aripiprazole reduces prolactin concentration in a dose-dependent manner because it is a dopamine-receptor partial agonist.
drugs most likely to cause hyperprolactinaemia
Risperidone, amisulpride, sulpiride, and first-generation antipsychotic drugs are most likely to cause symptomatic hyperprolactinaemia.
drugs least likely to cause hyperprolactinaemia
Hyperprolactinaemia is very rare with aripiprazole, asenapine, cariprazine, clozapine, and quetiapine treatment.
which drug reduces prolactin concentrations
Aripiprazole reduces prolactin concentration in a dose-dependent manner because it is a dopamine-receptor partial agonist.
Sexual dysfunction
Sexual dysfunction is reported as a side-effect of all antipsychotic medication; physical illness, psychiatric illness, and substance misuse are contributing factors. Antipsychotic-induced sexual dysfunction is caused by more than one mechanism. Reduced dopamine transmission and hyperprolactinaemia decrease libido; antimuscarinic effects can cause disorders of arousal; and alpha1-adrenoceptor antagonists are associated with erection and ejaculation problems in men. Risperidone, haloperidol, and olanzapine have a higher prevalence to cause sexual dysfunction. The antipsychotic drugs with the lowest risk of sexual dysfunction are aripiprazole and quetiapine.
Expert sources advise to consider dose reduction or discontinuation (where appropriate), or switching medication if sexual dysfunction is thought to be antipsychotic-induced.
drugs that have higher prevalence to cause sexual dysfunction.
Risperidone, haloperidol, and olanzapine have a higher prevalence to cause sexual dysfunction.
drugs that have lower prevalence to cause sexual dysfunction.
The antipsychotic drugs with the lowest risk of sexual dysfunction are aripiprazole and quetiapine.
Cardiovascular side-effects
Antipsychotic drugs are associated with cardiovascular side-effects such as tachycardia, arrhythmias, and hypotension. QT-interval prolongation is a particular concern with pimozide. Overall risk is probably dose-related but there is also a higher probability of QT-interval prolongation in patients using any intravenous antipsychotic drug, or any antipsychotic drug or combination of antipsychotic drugs with doses exceeding the recommended maximum.
Antipsychotic drugs with a low tendency to prolong QT interval include
aripiprazole, asenapine, clozapine, flupentixol, fluphenazine decanoate, loxapine, olanzapine, paliperidone, prochlorperazine, risperidone, and sulpiride.
Hypotension
Postural hypotension is a common cardiac side-effect of antipsychotic drugs, usually presenting acutely during the initial dose titration; however, it can also be a chronic problem. Postural hypotension can lead to syncope and dangerous falls related injuries, especially in the elderly. The second-generation antipsychotics most likely to cause postural hypotension are clozapine and quetiapine. Slow dose titration is commonly used to minimise postural hypotension.
The second-generation antipsychotics most likely to cause postural hypotension are :
clozapine and quetiapine.
lowest risk of diabetes of the antipsychotic drugs.
second-generation
amisulpride and aripiprazole
first generation
fluphenazine decanoate and haloperido
are antipsychotics weight neutral, weight loss or weight gaining drugs
weight gain
most likely to cause weight gain
Clozapine and olanzapine commonly cause weight gain.
least likely to cause weight gain
Amisulpride, asenapine, aripiprazole, cariprazine, haloperidol, lurasidone hydrochloride, sulpiride, and trifluoperazine are least likely to cause weight gain.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome (hyperthermia, fluctuating level of consciousness, muscle rigidity, and autonomic dysfunction with fever, tachycardia, labile blood pressure, and sweating) is a rare but potentially fatal side-effect of all antipsychotic drugs.
Expert sources advise discontinuation of the antipsychotic drug is essential for at least 5 days, preferably longer. The signs and symptoms of neuroleptic malignant syndrome should be allowed to resolve completely. Bromocriptine and dantrolene have been used for treatment.
treatment of Neuroleptic malignant syndrome
Bromocriptine and dantrolene have been used for treatment.
Long-acting depot injections can be considered for which patients
or patients with psychosis or schizophrenia who prefer such treatment after an acute episode or where avoiding non-adherence to antipsychotic medication is a clinical priority.
Antipsychotic depot injections asscoisated with less frequent Extrapyramidal reactions
aripiprazole, paliperidone, risperidone and olanzapine embonate.
monitoring requirements
Weight should be measured at the start of therapy with antipsychotic drugs, then weekly for the first 6 weeks, then at 12 weeks, at 1 year, and then yearly.
Fasting blood glucose, HbA1c, and blood lipid concentrations should be measured at baseline, at 12 weeks, at 1 year, and then yearly. Prolactin concentrations should also be measured at baseline.
Before initiating antipsychotic drugs, an ECG may be required, particularly if physical examination identifies cardiovascular risk factors (e.g. high blood pressure), if there is a personal history of cardiovascular disease, or if the patient is being admitted as an inpatient.
Blood pressure monitoring is advised before starting therapy, at 12 weeks, at 1 year and then yearly during treatment and dose titration of antipsychotic drugs.
Expert sources advise to monitor full blood count, urea and electrolytes, and liver function tests at the start of therapy with antipsychotic drugs, and then yearly thereafter.
risk of using multiple antipsychotics at once
sudden cardiac death
extrapyramidal effects
what should be considered if clozapine therapy of a sufficient dose is ineffective
non adherence
concurrent use of other drugs
where must clozapine patients be registered
clozapine patient monitoring service
why do 1st gen case more side effects
they are not selective for ant of the 4 dopamine pathways
1st gen drugs with higher risk of sedation
chlorpromazine, levomepromazine, promazine
1st gen drugs with lowest risk of sedation
haloperidol and benperidol
fluphenazine prochlorperazine, trifluoperazine
Higest risk of diabetes
CROQ CLOZAPINE RISPERIDONE OLANZAPINE QUETIAPINE
Drugs that cause Qt prolongation
Haloperidol and pizomide
