Psychosis
Psychosis

Psychosis

Psychosis is an impaired perception of reality, evidenced by the presence of one (or more) of the following thought disturbances:

  • Hallucinations
  • Delusions
  • Disorganised thinking, disorganised speech, or disorganised behaviour

Psychosis can be primary, meaning it results from a psychiatric disorder like schizophrenia, bipolar affective disorder, Parkinson’s, major depressive disorder. Or it can be secondary (previously termed organic psychosis), meaning it results from an organic medical cause or substance misuse. A psychotic disorder is any disorder that produces psychosis.

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Acute psychosis

Acute psychosis is a rapid worsening in psychotic symptoms, including severe delusions or hallucinatory experiences, that may result in psychomotor agitation and aggression. Psychosis-induced agitation and aggression are psychiatric emergencies where fast‐acting interventions are required.

🧰 Management:

  • Oral or IM benzodiazepines and/or antipsychotics - either given alone or in combination, are used for urgent pharmacological tranquillisation or sedation. This is important to resolve patient agitation which subsequently ensures patient and staff safety.
  • After managing patient agitation, an assessment can be completed to rule out an underlying medical condition.
  • Managing agitation (in acute psychosis):
    • Ensure patient and staff safety
    • Identify the underlying cause/medical condition - through relevant investigations
    • Attempt non-pharmacological de-escalation techniques - such as giving the patient space, open body language, calm verbal interaction with active listening, identifying the patient's emotions and expectations, and establishing clear and concise communication
    • Pharmacotherapy
    • Consider physical restraints - if the patient is refractory to de-escalation techniques and pharmacological options.

Causes

1️⃣
Causes of primary psychosis
  • Schizophrenia spectrum disorders
  • Mood disorders
  • Anxiety disorders
  • Personality disorders, such as
    • Schizotypal personality disorder (considered by the DSM-5 as part of the schizophrenia spectrum disorders).
      • This is a cluster A personality disorder that is characterized by eccentric behavior, an odd manner of dressing, magical or bizarre thinking/fantasies, strange beliefs, and/or anxiety and impaired capacity for social and interpersonal relationships.
    • Schizoid personality disorder
    • Paranoid personality disorder
2️⃣
Causes of secondary psychosis:
  • Multifactorial disorders, such as delirium
  • Autoimmune disorders, such as lupus cerebritis and anti-NMDA receptor encephalitis
  • Endocrine disorders, such as thyrotoxicosis, hypercortisolism
  • Metabolic disorders, such as porphyria, vitamin B12 (cobalamin), folate (B9), niacin (B3), thiamine (B1) deficiencies, Wilson disease
  • Neurological illness, such as dementia, TBI brain tumours, encephalitis, seizures
  • Chromosomal disorders, such as Klinefelter, Prader-Willi, DiGeorge syndrome
  • Substance-induced psychosis, such as
    • Recreational substances with psychoactive effects
      • Cannabis - the most common cause of substance-related psychosis
      • Alcohol
      • Hallucinogens; phencyclidine [PCP, angel dust], LSD, psilocybin [magic mushrooms], ketamine
      • Amphetamines; dextroamphetamine, levoamphetamine, and methamphetamine (meth)
      • Cocaine
    • Medications with adverse psychoactive effects
      • Analgesics; opioids
      • Sedatives or hypnotics; benzodiazepines, antidepressants, Z-drugs. (Sedative = hypnotic + anxiolytic drug)
      • & many more

⚠️ Risk factors

  • Stressful life events - such as bereavement, job loss, eviction, and relationship breakdown.
  • Childhood adversity - such as abuse, bullying, parental loss or separation.
  • Family heritage
  • Migration - especially from a developing country. There is an increased risk of schizophrenia.
  • Urban living
  • Substance use - including cannabis.
  • Medication use
  • Parental age - paternal age of >40 years and parental age of <20 years have both been associated with an increased risk of schizophrenia.
  • Exposure to the protozoan parasite Toxoplasma gondii - associated with a two-fold increase in risk of schizophrenia

😷 Presentation

💡 There may be clinical features associated with the underlying cause of the psychosis.

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Hallucinations

Hallucinations are perceptions of things that are not present, such as hearing absent sounds or seeing objects that aren’t actually there.

More formally: it is a perceptual abnormality in which sensory experiences [seeing, hearing, etc] occur in the absence of external stimuli being present.

Types:

  • Auditory (most common) - hearing things
  • Visual - seeing things
  • Somatic/tactile - bodily sensations
  • Gustatory - tasting things, often unpleasant or strange
  • Olfactory - smelling things
  • Hypnagogic - hallucinations that occur whilst going to sleep (whilst falling asleep) (sometimes seen in narcolepsy).
  • Hypnopompic - hallucinations that occur whilst waking up (whilst getting pomped up for the morning) (sometimes seen in narcolepsy).
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Delusions

Delusions is believing things that are obviously not real, such as believing that trees can talk or thinking you are superior and god-like (grandiosity).

Essentially they are a collection of fixed, false beliefs not attributable to a patient's culture or religion that are maintained (fixed) despite being contradicted by reality or rational arguments (has a debatable factual basis). They can be bizarre or nonbizarre.

So, delusions must:

  • Have a factual basis that is debatable
  • Be against/ out of socio-cultural norms
  • Have fixity

So we can determine if a thought is a delusion by targeting questions on the above 3 requirements.

  • Bizarre delusions - delusions that cannot be true or are inconsistent with the patient's social and cultural norms (ie a patient insisting that they can fly)
  • Non-bizarre delusions - delusions that can be true or are consistent with the patient's social and cultural norms (ie a patient insisting that they have won the lottery when this is not the case)

Types:

  • Persecutory - patient insists that they are being cheated on, conspired against, or harassed. This is the most common delusion.
  • Grandiosity - patient believes they have special powers or importance.
  • Delusions of reference - patient believes that normal things/ events are of special importance to them (such as thinking that the news reporter is talking directly to them/ about them).
    • Ideas of reference differ from delusions of reference in that insight is retained: the ideas are recognized by the individual as feelings that originate from within.
  • Paranoia - patient has an exaggerated distrust of others and is suspicious of their motives.
  • Erotomania - patient believes that other individuals are in love with them.
  • Jealousy - patient believes their partner is unfaithful without justification.
  • Somatic delusions - patient believes they are experiencing a bodily function or sensation when there is none present.
  • Mixed delusion - two or more delusions occurring simultaneously; no delusion is predominant over the other.
  • Unspecified delusion - a delusion that does not fit the criteria of other types or that cannot be clearly defined.
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Disorganised thinking, disorganised speech, or disorganised behaviour

Disorganised thinking/ disorganised thought refers to a disturbance in the logical connection between thoughts or the flow of thoughts.

Disorganised speech is a collection of speech abnormalities that lead to incoherent speech.

It is essential to understand that these are phenomena that may happen in psychotic patients, but they are not diagnostic.

Abnormalities of thought content:

  • Delusions
  • Obsessions - thoughts, images or impulses that occur repeatedly and feel out of the person’s control. The patient is aware these obsessions are irrational, but the thoughts continue to enter their head.
  • Compulsions - repetitive behaviours that the patient feels compelled to perform despite recognising the irrationality of the behaviour.
  • Overvalued ideas - a solitary, abnormal belief that is neither delusional nor obsessional but preoccupying to the extent of dominating the person’s life (e.g. the perception of being overweight in a patient with anorexia nervosa).
  • Suicidal thoughts
  • Homicidal/violent thoughts

Abnormalities of thought flow/stream & coherence:

  • Flight of ideas - quick succession of thoughts usually demonstrated in a continuous flow of rapid speech and abrupt changes in topic.
  • Circumstantial speech - nonlinear thought expressed as a long-winded manner of explanation, with multiple deviations from the central topic, before finally expressing the central idea
  • Clang association - use of words based on rhyme patterns rather than meaning. Common in mania (BPD).
  • Perseveration - the repetition of a particular response (such as a word, phrase or gesture) despite the absence/removal of the stimulus (ie a patient is asked what their name is, and they then continue to repeat their name as the answer to all further questions).
  • Thought-blocking - an objective observation of an abrupt stop/ending of a thought process, expressed as a sudden interruption in speech
  • Echolalia - involuntary repetition of another's words or sentences.

Abnormalities of thought possession:

  • Thought insertion - a belief that thoughts can be inserted into the patient’s mind.
  • Thought withdrawal - a belief that thoughts can be removed from the patient’s mind.
  • Thought broadcasting - a belief that others can hear the patient’s thoughts.

Abnormalities of thought form:

Thought form refers to the processing and organisation of thoughts. Some patients demonstrate abnormally fast (ie in a manic episode) or abnormally slow thought processing.

  • Loose associations - speech that is disconnected and fragmented, with the individual jumping from one idea to another unrelated idea. It's used interchangeably with derailment.
  • Tangential speech - the train of thought of the speaker wanders and shows a lack of focus, never returning to the initial topic of the conversation.
    • Unlike loose associations, where there may be abrupt shifts between unrelated topics without a clear connection, tangential speech tends to maintain some thematic relevance or association between topics, even though the progression is not logical or coherent.
  • Neologisms - the creation of new words with idiosyncratic meanings.
  • Word salad (incoherence) - speaking a random string of words without relation to one another.

Disorganised speech can involve changes to the rate, quantity, tone, volume, fluency and rhythm of speech:

Rate of speech:

  • Pressured speech - accelerated thoughts that are expressed as rapid, loud, and voluminous speech, often in the absence of social stimulation. Can be present in mania.
  • Slow speech - may occur due to psychomotor retardation, typically associated with depression.

Quantity of speech:

  • Poverty of speech (alogia) - associated with depression.
  • Excessive speech - associated with mania.

Tone of speech:

  • Monotonous speech - associated with conditions such as depression, psychosis and autism.
  • Tremulous speech - associated with anxiety.

Volume of speech:

  • Quiet speech may be seen in depression.
  • Loud speech can be seen in mania.

Fluency and rhythm of speech:

  • Stammering or stuttering
  • Slurred speech - may occur in major depression due to psychomotor retardation. It may also be a sign of acute intoxication.
  • Stilted speech - can be a manifestation of thought blocking.

🔍 Investigations

  • Thorough history (including MSE) and physical examination
  • Lab studies (to identify any abnormalities that may indicate an underlying cause):
    • FBC
    • Liver function tests
    • Basic metabolic panel - includes sodium, potassium, chloride, bicarbonate, urea nitrogen, creatinine, and glucose.
    • Thyroid function tests
  • Other blood tests may be considered based on clinical judgement, such as testing for vitamin deficiencies or drug toxicities.
  • MRI or CT head may be indicated

🧰 Management

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Management of psychosis in primary care
  • Suspect psychosis in people who present with:
    • Positive symptoms such as hallucinations and delusions.
    • Negative symptoms explained in schizophrenia.
  • Recognise the prodromal phase which may last for a few days up to 18 months.
    • ⭐️ It is characterised by increasing distress and a decline in personal and social functioning
    • May include low-intensity psychotic symptoms that usually last less than 1 week. May include hallucinations/unusual perceptual experiences, unusual thoughts (including new preoccupation with mystical or religious themes, concerns about being under surveillance, etc)
    • May include reduced interest in daily activities like failure to maintain hygiene
    • May include problems with mood, sleep, memory, concentration, communication, affect, motivation
    • May include features of depression, anxiety or irritability
    • May include incoherent or illogical speech
  • Hold a low threshold for patients exhibiting the above symptoms with a positive family history (1st degree) of psychosis and/or schizophrenia

Once an individual is identified to be at risk, a risk assessment of harm to the patient and/or others should be done.

  • Determine the level of risk to the person by enquiring about/considering:
    • History of self-harm.
    • Suicidal ideation and plans, any previous attempts.
    • Feelings of hopelessness.
    • Misuse of recreational drugs and/or alcohol.
    • The likelihood of accidental or non-accidental injury.
    • Whether the person is experiencing 'command' hallucinations and whether they feel compelled to act upon them.
    • Level of family/social support.
    • Timing — be aware that the highest risk of suicide tends to be around the time of a psychotic episode and shortly after hospital discharge.
  • Determine the risk of harm to others by enquiring about/considering:
    • The potential for neglect of individuals dependent on the person for care, in particular family, children, and any other dependents. 
    • Any risk to the public, especially if there is a previous history of confrontation with others, violence, carrying weapons, and use of stimulant drugs.
    • Whether the person is experiencing delusions focused on a particular individual.
  • Refer to psychosis intervention services as appropriate.
  • People at risk will usually get CBT and management of concurrent medical conditions.
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Antipsychotics

Antipsychotics are classified as 1st generation (typical antipsychotics) or 2nd generation (atypical antipsychotics) antipsychotics.

1st generation antipsychotics are thought to work by blocking the D2 receptors in the brain. 2nd generation antipsychotics act on a wider range of receptors (including D2, 5HT2, muscarinic, histamine, alpha adrenoreceptors, and others). The effect on these receptors is what leads to extrapyramidal symptoms (EPS).

Generally, 2nd generation antipsychotics have fewer EPS compared to first generation antipsychotics. However, they have other important adverse effects, such as arrhythmias, weight gain, sexual dysfunction, glucose intolerance, hyperprolactinaemia (which is why prolactin levels are checked routinely).

Benperidol
Amisulpride
Chlorpromazine
Aripiprazole
Flupentixol
Clozapine
Haloperidol
Olanzapine
Levomepromazine
Paliperidone
Pericyazine
Quetiapine
Perphenazine
Risperidone
Pimozide
Zotenpine
Prochlorperazine
Promazine
Sulpride
Trifluoperazine
Zuclopenthixol

Antipsychotics can be given orally or as depot injections. Antipsychotic depot injections are used for maintenance therapy when adherence to oral treatment is unreliable. They are administered every 1–4 weeks.

There is no 1st line antipsychotic drug that suits all psychotic people. So, the choice is multifactorial depending on the person's personal choice, medication history, degree of sedation required, risk of particular adverse effects, and the degree of negative symptoms (usually these are improved better with 2nd gen antipsychotics).

The only exception is clozapine, which is significantly more effective than all other antipsychotics, and hence is offered to people who do not respond adequately to 2 other antipsychotics.

  • ⭐️ The most common side effect of clozapine is constipation (due to inhibiting peristalsis)
  • Drowsiness
  • Agranulocytosis (1%) and neutropenia (3%) - as such FBC monitoring is necessary every month.
  • Reduced seizure threshold - can induce seizures in up to 3% of patients
  • Myocarditis - a baseline ECG should be taken before starting treatment
  • Hypersalivation
  • Hypertension or postural hypotension
  • Weight gain
  • Smoking cessation can increase clozapine blood levels

💡 It is recommended to measure a clozapine level in the presence of an infection in anticipation of toxicity.

💡 Blood lipids, bloods glucose, and weight should be regularly checked (baseline, after a few months, and then yearly) - for all antipsychotics

Adverse effects:

  • EPS - more common with 1st gen antipsychotics:
    • Dystonic reactions - abnormal spasms of the face and body [usually within the 1st 1-5 days] like torticollis or oculogyric crisis. Can be alleviated with anticholinergic drugs like procyclidine or biperiden
    • Pseudoparkinsonism (tremor, bradykinesia, and rigidity) (usually 1-4 weeks after initiating Rx). Can be alleviated with anticholinergic drugs like procyclidine
    • Akathisia - a feeling of inner restlessness and inability to sit still [usually 1-2 months after initiating Rx]. Can be relieved by lowered the medication dose, B blockers, benztropine, BZD's
    • Tardive dyskinesia - a late-onset movement disorder that can occur with prolonged use of antipsychotics (usually months-years after initiating the medication).

      • TD is thought to be caused by long-term blockade of dopamine receptors in the nigrostriatal dopamine pathway, causing receptor upregulation (ie, increase in number) and compensatory supersensitivity of postsynaptic neurons.

      It is characterised by rhythmical, involuntary movements, usually lip-smacking and tongue rotating (orofacial dyskinesia), although it can affect the limbs and trunk.

      It may be persistent and can sometimes worsen on treatment withdrawal.

  • Neuroleptic malignant syndrome - a rare but potentially fatal adverse effect of all antipsychotics. It tends to happen a few days after starting the medication. Tetrad: hyperthermia, muscle rigidity, autonomic instability (hypotension, tachycardia, sweating, etc), altered mental status (confusion, fluctuating consciousness). Bloods: raised LFT's, WCC, CK. Management involves stopping the causative medications and supportive care (e.g., IV fluids and sedation with benzodiazepines). Severe cases may require treatment with bromocriptine (a dopamine agonist) or dantrolene (a muscle relaxant).
  • Weight gain - common in all antipsychotics but more so in 2nd gen. In general, clozapine and olanzapine have the greatest potential to cause weight gain, followed by chlorpromazine, quetiapine, and risperidone.
  • Hyperprolactinaemia - with most antipsychotics, and may lead to galactorrhoea, amenorrhoea, gynaecomastia, hypogonadism, sexual dysfunction, and an increased risk of osteoporosis.

    • This is due to antipsychotics disrupting the tuberoinfundibular pathway, which connects the hypothalamus to the pituitary gland and is responsible for the tonic inhibition of prolactin secretion.

  • Dyslipidaemia
  • Sedation - performance of skilled tasks (such as driving) may be affected and the effects of alcohol are enhanced.
  • Anticholinergic effects (dry eyes, dry mouth, dry skin, urinary retention, constipation, skin flushing)
  • Impaired glucose tolerance - more common in people with schizophrenia
  • QT interval prolongation - the most widely reported cardiac conduction defect
  • VTE
  • Neutropenia - stop the suspected drug if neutrophils fall below 1.5 x 109/L
  • Abnormal LFTs - stop the suspected drug if LFTs suggest hepatitis (transaminases rise to 3 times normal) or PT or albumin are abnormal
  • Photosensitivity
  • DRESS
  • Pneumonia - unclear mechanism
  • Diplopia - uncommon
  • Restless leg syndrome - uncommon

Specific to a certain antipsychotic:

  • Sleep apnoea syndrome - with quetiapine
  • Cardiomyopathy, myocarditis and cutaneous vasculitis - with quetiapine, but a causal relationship has not been established
  • Increased stroke risk in dementia patients - olanzapine and risperidone are associated with an increased risk of stroke in elderly people with dementia