CNS E-book Flashcards
Bipolar disorder and mania - aetiology
Potential causes include genetic factors, environmental factors, biochemical factors, endocrine factors, physical illness (e.g. diabetes and thyroid disease) or the side-effects of medication (e.g. antihypertensives, benzodiazepines).
Bipolar disorder and mania - Epidemiology
Lifetime prevalence of developing a bipolar disorder I is 1% and 0.4% for bipolar disorder II; Average age of onset: late adolescence; Bipolar disorder I occurs equally in both sexes. There is disputed evidence that bipolar disorder II is more common than in women than in men.
Bipolar disorder and mania - Clinical features
The Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-V) and the International Classification of Disease (ICD-10) describe the diagnosis criteria for bipolar disorder. DSM-V makes a distinction between bipolar
disorder I where people have “full blown manic episodes (commonly interspersed with episodes of major depression)” and Bipolar disorder II where people may
experience “depressive episodes and less severe manic symptoms, classed as hypomanic episodes.”
Mania - Disinhibition, grandiose ideas, flamboyant
clothing, bright and excessive make-up. Less severe mania is termed hypomania
Bipolar disorder and mania - diagnosis
DSM-V states that at least one episode of mania is required for diagnosis of bipolar disorder I (depression is not essential) and at least one at least one major depressive episode and at least one hypomanic episode for bipolar disorder II. ICD-10 states that at least 2 mood episodes are required for diagnosis – one which must be mania or hypomania. ICD-10 does not provide specific criteria for bipolar disorder II.
Bipolar disorder and mania -Investigations:
Full history and corroborative history from family member or carer if possible; Late presentation may be similar to symptoms of schizophrenia; Exclude hypothyroidism, cerebrovascular insults or dementia, especially if over 40 years old.
Bipolar disorder Management in primary care
NICE CG185 recommends patients are urgently referred for a specialist mental health assessment if mania or severe depression is suspected or they are a danger
to themselves or others.
To manage depressive symptoms in bipolar disorder patients in primary care should be offered a psychological intervention that has been developed specifically for bipolar disorder or high intensity psychological intervention (cognitive behavioural therapy, interpersonal therapy or behavioural couple’s therapy).
Lithium should not be started in primary care in patients who have not taken it before (unless there are shared care arrangements).
Valproate should not be started in primary care.
Management of Bipolar depression
To manage depressive symptoms in bipolar disorder patients in secondary care should be offered a psychological intervention that has been developed specifically for bipolar disorder or high intensity psychological intervention (cognitive behavioural therapy, interpersonal therapy or behavioural couple’s therapy). In patients with moderate to severe depressive symptoms consider fluoxetine combined with olanzapine or quetiapine on its own. If the person prefers, consider either olanzapine (without fluoxetine) or lamotrigine on its own. If there is no response to fluoxetine combined with olanzapine, or quetiapine, consider lamotrigine on its own.
Pharmacological options in mania and hypomania
Pharmacological treatments are used short term in secondary care to treat episodes of mania or hypomania. If an individual is taking an antidepressant and develops
mania or hypomania it should be considered whether to stop the antidepressant.
If a person develops mania or hypomania and is not taking an antipsychotic or mood stabiliser, NICE CG185 recommends haloperidol, olanzapine, quetiapine or
risperidone, taking into account any advance statements, the person’s preference and clinical context (including physical comorbidity, previous response to treatment
and side effects).
If the initial antipsychotic medication is ineffective or unacceptable (for example, due to side effects) an alternative medication out of one of those listed could be tried instead.
If the alternative antipsychotic is not effective at the maximum licensed dose, lithium could be tried as an addition. If adding lithium is not effective, or if lithium is not suitable (for example, because the person does not agree to routine blood monitoring), consider adding valproate instead.
NICE CG185 does not recommend lamotrigine is used to treat mania.
Valproate
Valproate available as sodium valproate (e.g. Epilim), valproic acid (e.g. Convulex), and semisodium valproate (e.g. Depakote). Products have different licenced indications. Semisodium and sodium valproate are metabolised to valproic acid, which is responsible for the pharmacological activity of all three preparations.
Valproate should not be used by women of childbearing age to treat long term or acute episodes of bipolar disorder.
Valproate must no longer be used in any woman or girl able to have children unless she has a pregnancy prevention programme in place. This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant. This guidance was updated in January 2018 when the MHRA strengthened its advice on
the risk of abnormal pregnancy outcomes.
Lithium
Lithium is an alkaline metal element that occurs naturally as the mineral petalite.
• It is a mood stabiliser – the term refers to the ability to treat one or both ‘poles’ of bipolar disorder without causing a switch to the other pole (in comparison
antidepressants which can cause a switch to mania).
• The mode of action not understood: May exert its effects via one or more of a variety of mechanisms
• Do not start unless continuing for at least 3 years – short term use may worsen the course of the illness
• Usually takes at least a week to achieve a response
• Abrupt discontinuation leads to rebound mania – time to recurrence of affective disorder (mostly mania) - 3 months for 50% of patients
• To reduce risk of relapse – decrease dose of lithium gradually over 1 month.
• Individual lithium preparations are not bioequivalent so cannot be substituted
• Narrow therapeutic index: Side-effects directly related to plasma levels
o >1mmol/L: transient mild GI symptoms, fine hand tremor, thirst, polyuria, hypothyroidism, mental dulling, nephrotoxicity.
o Toxicity: >1.5 mmol/L anorexia, nausea and vomiting,muscle weakness and twitching, drowsiness;
o >2 mmol/L disorientation, seizures, coma and death
• Interactions
o Diuretics reduce renal clearance of lithium - Thiazides are the worst culprits, loop diuretics are somewhat safer.
o NSAIDs can increase serum lithium levels by up to 40% - related to effect of NSAIDs on fluid balance. Particularly important if prn NSAID added to longstanding lithium
o Haloperidol if added to lithium and increased rapidly to very high doses can cause severe neurotoxicity, but in practice widely prescribed and very useful combination
o Carbamazepine often used in refractory illness
o SSRIs- useful combination, any interaction rare
o ACEI and A2RAs decrease excretion of lithium, and can precipitate renal failure – extra care needed in monitoring
• Evidence base - 60-80% effective in acute mania. Probably effective in bipolar depression but confounding data– cross-over designs incorporating abrupt switching to placebo therefore rebound mania.
• Evidence strong for reducing suicidality in bipolar disorder. Estimated that 15% of those with bipolar illness take their own life. Mortality from physical illness is also increased. Chronic treatment with lithium reduces mortality from suicide to the same level as that seen in the general population. Mortality from other causes probably not altered
Lithium Patient counselling points
- Women of child-bearing age should use reliable contraception
- Be aware of symptoms of toxicity, why they might occur and what to do
- Bouts of vomiting and diarrhoea will lead to sodium depletion, which will increase plasma lithium concentration
- Salt-free diet is contraindicated
- Maintain adequate fluid balance
- Do not double the dose if you miss a tablet
Long term management of bipolar disorder (Preventing relapse)
Medication taken during episodes of mania or bipolar depression should be considered when planning long-term pharmacological treatment to prevent relapse.
The patient may prefer to remain on this treatment or switch to lithium
Lithium is most effective for long-term pharmacological treatment for bipolar disorder and should be used first-line.
If lithium cannot be taken, for example, it’s poorly tolerated or it’s not suitable, consider valproate or olanzapine instead or, if it has been effective during an episode of mania or bipolar depression, quetiapine.
what is schizophrenia
Schizophrenia is a psychotic ‘syndrome’ identified by a characteristic cluster of symptoms that last for a certain time, the presentation of which is extremely varied. It
is a disease of neural disconnection and includes a group of illnesses diverse in nature, covering a broad range of perceptual, cognitive and behavioural disturbances.
Psychosis and schizophrenia - Epidemiology
- Prevalence estimated between 0.2% and 0.7%
- More frequent in people born in cities – the larger the city and the longer the person has lived there the greater the risk
- It is more common in migrants e.g. rate of schizophrenia in African-Caribbean people living in the UK are 6 – 8 times higher than those of native white population
- Incidence about 1 - 2 new cases per 10,000 population per year
- Incidence roughly the same in men and women
- Peak age of onset: Men 21 - 26 years, women 25 – 32 years
- Life expectancy reduced by 15 years- mainly due to cardiovascular disease, 1 in 20 commit suicide
Psychosis and schizophrenia - Aetiology
There are various models of causality (see box 3.1) but other factors are involved e.g. migration, infections, viruses, toxins etc. (i.e. it is a multi-factorial disorder):
• Greatest risk factor- positive family history
• Lifetime risk in general population less than 1%;the risk is 6.5% in first degree relatives and greater than 40% in monozygotic twins of affected people
• People probably inherit several risk genes, which interact with each other and the environment to cause schizophrenia once a critical threshold is crossed
• Patients are more likely to have experienced obstetric complications e.g. premature birth, then in adulthood different environmental stressors e.g. social isolation, migrant status, and urban life
• Those with supportive parents once diagnosed do much better than those with critical or hostile parents
• Cocaine and amphetamines- can induce a clinical picture similar to paranoid schizophrenia- also cannabis implicated (maybe a genetically determined vulnerability to the environmental stressor i.e. cannabis)
Models of causality in schizophrenia
Vulnerability model: stress precipitator, depending on personality, social network or environment
Developmental model: prenatal and perinatal development key – also adolescence
Ecological model: external factors – social and cultural factors e.g. population density, socio-economic and racial status etc.
Genetic model: higher incidence in siblings
Transmitter abnormality model: dopamine theory
schizophrenia Clinical Features - positive symptoms
- Characterised by acute onset, good response to neuroleptics and better outcome
- Lack of insight
- Hallucinations – auditory most common but all senses affected
- Delusions e.g. persecution or controlled by external force
- Thought disorder – distorted or illogical speech, no logical chain of thought
schizophrenia Clinical Features - negative symptoms
- Characterised by slow insidious onset, relative absence of acute symptoms, poor neuroleptic response
- Social withdrawal
- Apathy
- Self neglect
- Emotional blunting
- Paucity of speech
- Loss of motivation and initiative
- Social / occupational dysfunction
Investigations schizophrenia
- Diagnostic classification: DSM IV, ICD 10 (see box 3.3)
- Rating scales to assess symptoms: e.g. Brief Psychiatric Rating Scale; Scales for the Assessment of Positive/Negative Symptoms (SAPS, SANS); Positive and Negative Syndrome Scale (PANSS)
- Screening questions: E.g. “Do you hear voices when no one is around? What do they say?”, “Do you ever think that people are talking or gossiping about you, maybe even thinking about trying to get you?”, “Do you ever think that somehow people can pick up on what you are thinking or can manipulate what you are thinking?”
- Spectrum of disorders etc. – e.g. schizoaffective disorder, personality disorders etc.
- Prognosis: 15-20% recover completely, 70% relapse and may develop mild to moderate negative symptoms, 10% will become seriously disabled.
ICD-10 Diagnostic criteria
At least one of the following present most of the time for a month:
• Thought echo, insertion or withdrawal, or thought broadcast
• Delusions of control referred to body parts, actions or sensations
• Delusional perception
• Hallucinatory voices giving a running commentary, discussing the patient, or coming from some part of the patient’s body
• Persistent bizarre or culturally inappropriate delusions
Or at least two of the following present most of the time for a month:
• Persistent daily hallucinations accompanied by delusions
• Incoherent or irrelevant speech
• Catatonic behaviour such as stupor or posturing
• Negative symptoms such as marked apathy, blunted or incongruous mood
If the onset of psychosis is suspected
If the onset of psychosis is suspected, the patient should be referred rapidly to secondary care – early intervention team, crisis resolution or home treatment teams, early intervention services, assertive outreach teams or community mental health team. A psychiatrist needs to confirm presence of psychotic symptoms. The need for
hospital admission or use of the Mental Health Act (e.g. to section the patient) will depend on their presentation, risk assessment and the availability of good community support. Prompt identification and treatment may lead to an improved outcome.
Management of acute episodes schizophrenia
First episode psychosis and acute exacerbations or recurrence of psychosis or schizophrenia are treated in the same way:
• Offer oral antipsychotics, the choice of which should be made by the service user and healthcare professional together. Information should be provided about the likely benefits and side effects of each drug
• Offer psychological interventions (family intervention and individual CBT)
• Psychological interventions are more effective when delivered in conjunction with an antipsychotic
Before starting antipsychotic medication, the following baseline investigations should be recorded:
• Weight
• Waist circumference
• Pulse and blood pressure
• Fasting blood glucose, HbA1c, blood lipid profile, prolactin levels
• Assessment of movement disorders
• Assessment of nutritional status, diet and level of physical activity
• Antipsychotic medication should be used at optimum dosage for 4-6 weeks before review (Maudsley suggests an affect will be apparent within 2-3 weeks at an effective dose).
• Do not use loading doses or prescribe antipsychotics concurrently except for short change over periods
• Monitor regularly: NICE recommends clozapine should be offered to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least 2 different
antipsychotic drugs. At least 1 of the drugs should be a non-clozapine second-generation antipsychotic (Maudsley recommends one should be
olanzapine).
• Continue on antipsychotic for 1-2 years; withdraw gradually
• Monitor for relapse for 2 years after acute episode
• In schizophrenia – antipsychotic essential, psychosocial treatment after recovery
• Remember to consider adherence: poor tolerability - switch drug; poor memory/ compliance aids; lack of insight – depot
General principles of prescribing - schz
• Use lowest possible dose known to be effective
• Use of a single antipsychotic (with or without additional mood stabiliser or sedatives) is recommended for the majority of patients
o Polypharmacy of antipsychotics only when response clearly inadequate to single therapy (including clozapine) – risk of prolonged QT interval
• Antipsychotics should not be used as ‘prn’ sedatives
• Assess response by recognised rating scales
• Do not recommend increasing dose of antipsychotics above recommended maximum dose – not evidence-based, rarely worthwhile and associated with increased risk of adverse drug reactions
• Titrate dose to lowest known to be effective - Dose increases should then take place only after 2 weeks of the patient clearly showing a poor response or no response
• With depot medication, plasma levels rise for 6-12 weeks after initiation, even without a change in dose - Dose increases during this time are therefore inappropriate
Pharmacological options - schz 1st gen
First Generation Antipsychotics (FGAs) – drugs introduced to market prior to 1990
- Phenonthiazines:
• Aliphatic phenothiazines e.g. chlorpromazine
• Piperazine phenothiazines e.g. fluphenazine, trifluoroperazine
• Piperidine phenothiazines e.g. piotiazine - Butyrophenones e.g. Haloperidol
- Thioxanthenes e.g. Flupenthixol
- Benzamides e.g. sulpiride
- Diphenylbutylpiperidines e.g. pimozide
Pharmacological options - schz 2nd gen
Second Generation Antipsychotics (SGAs) – drugs introduced to market post 1990
- Amisulpiride
- Aripiprazole
- Asenapine
- Brexpiprazole
- Cariprazine
- Iloperidone
Lurasidone
Olanzapine
Quetiapine
Risperidone
Sertindole
Ziprasidole
First Generation Antipsychotics (FGA)
As a class more likely to cause extra-pyramidal side effects (EPSEs / EPS) than SGAs. • Phenothiazines: subdivided into 3 groups based on their basic chemistry o Aliphatic phenothiazines e.g. chlorpromazine most sedating, Chlorpromazine also causes photosensitivity reactions (use sun block), and can occasionally cause a hypersensitivity reaction resembling obstructive jaundice, also lowers seizure threshold in a dosedependent fashion. Moderate antimuscarinic and extra-pyramidal side effects (EPSEs). o Piperazine phenothiazines e.g. trifluoroperazine least sedative but more pronounced EPSEs • Butyrophenones: e.g. Haloperidol o studies show optimal response around 10-12 mg/day and higher doses now rare • Thioxanthines: Flupentixol usually prescribed as a depot • Diphenylbutylpiperidines: Pimozide only one still prescribed (but rarely), narrower side-effect profile but was associated with sudden death so if on dose above 16mg need periodic ECGs • Substituted benzamides: Some question whether sulpiride is a typical or an atypical – hence why FGA / SGA was a better classification.
