Schizophrenia: Types, Symptoms, Diagnosis and Treatment

The term Schizophrenia is derived from two Greek words: skhizo (to split) & phren (mind) meaning, the split between the emotions & the intellect. Schizophrenia is a clinical syndrome which exists as a constellation of symptoms such as:

  • hallucinations
  • delusions,
  • decreased affect,
  • disorganized behaviour,
  • impaired functioning etc.

Though Schizophrenia affects both men & women equally, its onset is reported to be earlier in men than in women. Average age of onset is 18 years in men and 25 years in women.

Positive Symptoms of schizophrenia 

  1. Hallucinations
  2. Delusions
  3. Combativeness
  4. Insomnia
  5. Disorganized speech
  6. Disorganized behaviour
  7. Thought disorder

Hallucinations

This is a perception disturbance in sensory experiences of the environment which can be can be auditory, visual, olfactory, or tactile with auditory hallucinations being the most common.

Delusions

This is incorrect or false belief possibling on religious, paranoid/persecutory, grandiose, somatic, influential or sexual. Among these, paranoid/persecutory delusions are the most common.

Negative Symptoms of schizophrenia 

  1. Alogia
  2. Flat affect or affective flattening
  3. Apathy
  4. Lack of motivation to engage in any activity
  5. Social withdrawal
  6. Poor attention
  7. Anhedonia

Diagnosis of Schizophrenia

To diagnose Schizophrenia, a patient must have at least two of the following symptoms:

  • delusions,
  • hallucinations,
  • disorganized speech or catatonic behaviour (grossly disorganized behaviour), &
  • negative symptoms

Again, the symptoms should be present for at least 1 month, with at least 6 monthsof continuous prodromal or residual symptoms. In addition, at least one area of the patient’s social or occupational functioning should besignificantly affected. Other conditions causing similar symptoms such as schizoaffective disorder,mood disorders, substance abuse, & general medical conditions should be ruled out.

Clinical Evaluation

Clinical evaluation of schizophrenia includes consideration of:

  1. Psychiatric history
  2. Mental status examination
  3. General medical screening which includes laboratoryinvestigation
  4. Treatment plan
  5. Monitoring & follow-up

Types of Schizophrenia 

Schizophrenia can be classified into the following

  1. Paranoid
  2. Disorganized
  3. Catatonic
  4. Undifferentiated
  5. Residual

Paranoid

Paranoid is the most common type of schizophrenia. Here, there is prominent preoccupation with delusions and hallucinations. However, cognitive function is usually preserved; if thought disorder is present, it does not prevent description of delusions or hallucinations.

Disorganized

In this type of schizophrenia, a patient tends to have disorganized speech & behaviour with a flat affect. Hallucinations & delusions are not well formed & fragmented. The patient may also have bizarre mannerisms & grimacing.

 Catatonic

In catatonic schizophrenia, motor symptoms are most noticeable. There may be rigid immobility or excessive purposeless movements. The patient may be silent & withdrawn or may become loud & shout. Bizarre voluntary movements such as posturing may also occur. The patient may fluctuate between the two extremes.

Undifferentiated

Here, patients meet the criteria for a diagnosis of schizophrenia but do not meet the criteria for a specific type. The patients may meet the criteria for multiple types of schizophrenia. No one type appears to be dominant. No clear prominence of a particular constellation of symptoms.

Residual

Here, the patient does not have acute psychosis, but some symptoms of schizophrenia remain. In addition, there is an absence of prominent symptoms but ongoing disturbance of less magnitude. Moreover, largely negative symptoms are seen. Example include flat affect, social withdrawal, & loose associations. Prominent delusions or hallucinations are not present.

Treatment Goals and Objectives

There is currently no known cure for schizophrenia. Treatment options include Psychotherapy & Pharmacotherapy and the goals and Objectives of these include:

  1. To minimize symptoms of schizophrenia
  2.  To improve quality of life & social/occupational functioning
  3. To prevent relapse & hospitalization
  4.  To minimize adverse effects of medications
  5. To prevent suicide attempts or self-harm

Causes of Schizophrenia

The actual cause of Schizophrenia remains unknown, but there are many theories & models

  1. Vulnerability Model – Vulnerability can depend on premorbid personality, social network or the environment & is triggered by some stress. Manipulation & avoidance of such stress can abort a potential Schizophrenic episode.
  2. Developmental Model – Postulates that there are critical periods in the development of neuronal cells which, if adversely affected, may result in Schizophrenia. Supported by neuroimaging studies which show structural brain abnormalities in patients with Schizophrenia.
  3. Ecological Model – Postulates that external factors involving social, cultural & physical forces in the environment. e.g. population density, individual space, socio-economic status & racial status. The evidence for the support of this model is weak.
  4. Genetic Model – Higher incidence in the siblings of Schizophrenics. However, even in monozygotic twins there are many cases where only one sibling has developed Schizophrenia.
  5. Transmitter abnormality Model – Postulates that Schizophrenia is caused primarily byan abnormality of dopamine receptors (& in particular, D2-receptors)
  6. Other factors involved in Schizophrenia – Migration, perinatal insult, infections, season of birth, family environment etc. have been implicated.

Pharmacotherapy: Anti-psychotic Medications

Drugs do not cure Schizophrenia & are only partially effective at eradicating some symptoms such as delusions & negative symptoms. Except for clozapine & other atypicals anti-psychotics, there is little evidence for antipsychotic drugs being of value in the treatment of negative symptoms. This claim, however remains controversial.
Two generations of antipsychotic medications are available for treatment:

  1. First-generation (Typical) antipsychotics
  2. Second-generation (Atypical) antipsychotics

Mechanism of Action of Antipsychotics

The First-generation also known as typical antipsychotics are potent Dopamine 2 receptor blockers. Antipsychotic effect is primarily mediated through the blockade of dopamine type 2 (D2) receptors.

Potency of Antipsychotics

The potency of antipsychotics can either be High, moderate, or low.
High-potency agents have higher affinity for the dopamine receptor with higher risk for development of extrapyramidal symptoms (EPS).
Low-potency agents have less affinity for dopamine receptors with less risk for causing EPS. These have more adverse effects from their activity at histamine, muscarinic & α-receptors.

Efficacy

When dosed in equivalent doses, the various typical antipsychotics have similar efficacy. Equivalent doses are described using chlorpromazine (CPZ) equivalents. Typical antipsychotics are thought to be as effective as atypical antipsychotics for positive symptoms but are less effective for negative symptoms. In general, typicals are effective in treating positive symptoms while atypicals treat both positive & negative symptoms with minimal risk of EPS.

Adverse Effects

The adverse effects of antipsychotcs can be determined by their receptors affinities:
Dopamine: Extrapyramidal symptoms, hyperprolactinaemia
Histamine: Sedation, weight gain
Muscarinic: anticholinergic adverse effects, cognitive impairment, tachycardia
Alpha: Orthostatic hypotension, reflex tachycardia
Serotonin: Weight gain

Extra-pyramidal side effects (EPS)

EPS can occur with all the typical antipsychotics, especially with high potency typical antipsychotics. There are four types of EPS which are

  1. Acute dystonia
  2. Akathisia
  3. Pseudo-parkinsonism – acute dystonia, akathisia & pseudo-parkinsonism are early-onset symptoms which occur within the 1st 4 weeks of therapy.
  4. Tardive dyskinesia

Acute Dystonia
Acute dystonia describes sudden spasms that primarily occur in the eye, neck, face & throat muscles. This can be a medical emergency. It may present as grimacing & facial distortion, neck twisting & laboured breathing; oculogyric crisis, occasionally. It can occur within hours of initiating the medication or increasing the dose. The use of an IV or IM treatment may be warranted for quick symptom resolution. It is common in patients using high doses of high potency typical antipsychotics.
Management of dystonia
Anticholinergic agents like benztropine (2mg), & diphenhydramine (IV, 50 mg) can be used. Prevention of future reactions can be achieved by decreasing the antipsychotic.
Akathisia (or motor restlessness)
Akathisia is described as an inner restlessness associated with feelings of having to move. It causes patient to pace up & down, and unable to sit still, or to constantly shift their legs position or tap their feet
Treatment of Akathisia
Akathisia can be prevented or reduced through dose reduction of antipsychotic, lipophilic β blockers or benzodiazepines. Alternatively, therapy may be changed to an atypical antipsychotic.
Pseudo-parkinsonism
Clinically, pseudo-parkinsonism appears similar to idiopathic Parkinson disease & includes symptoms like: tremor, rigidity (or akinesia), and masklike face. Cogwheel rigidity is as a result of the presence of both tremor & rigidity. Drugs that block dopamine receptors should be expected to produce effects similar to those seen in Parkinson’s disease. Other common symptoms: Drooling & excessive salivation; a shuffling gait; fatigue when performing repetitive motor activities.
Treatment entails changing to an atypical antipsychotic, decreasing the dose, and/or adding an anticholinergic agent.
Tardive dyskinesia 
This is a movement disorder that can occur in various locations of the body: face, tongue, hips, neck & extremities. The movements can be dystonic (fixed) or choreoathetoid (rhythmic) with common movement disorders being: tongue chewing, lip smacking & rhythmic movements of the trunk.
Tardive dyskinesia may be irreversible, therefore patients taking antipsychotics should be monitored closely for any movement disorders. A tool such as Abnormal Involuntary Movement Scale (AIMS) is available to assist in monitoring Tardive dyskinesia. Vigilant monitoring for signs of Tardive dyskinesia is the best way to prevent it from occurring.
Factors which appear to be associated with Tardive dyskinesia include:

  1. typical antipsychotic drugs
  2. the co-prescribing of anticholinergic drugs
  3. the co-prescribing of lithium
  4. advanced age
  5. prior experience of acute EPS
  6. brain damage

Other factors with unproven associations which is believed to cause Tardive dyskinesia include: depot formulations of antipsychotic drugs; dosage of antipsychotic drug; antipsychotic drugs with high anticholinergic activity.
Treatment of Tardive dyskinesia
Multiple treatments options have been attempted to treat Tardive dyskinesia, although none have been proven to be effective & are rarely successful. These include:

  • dopamine-depleting agents e.g. reserpine, tetrabenazine
  • GABA mimetic agents e.g. sodium valproate & baclofen
  • benzodiazepines
  • cholinergic agents e.g. choline & lecithin
  • methyldopa which interferes with catecholamine synthesis
  • the provision of drug holidays (the risks of drug holidays outweigh the benefits clinically)
  • Vitamin E
  • gradual withdrawal of the typical antipsychotic drug & replacement with an atypical antipsychotic drug – this is the most current strategy.

Typical Antipsychotics

Mechanism of Action

With the exception of aripiprazole, the atypical antipsychotics are dopamine antagonists but also potently block 5HT2-receptors, especially 5HT2A-receptors. They block 5-HT to a greater extent than dopamine.

Typical Agents

  • Clozapine
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Ziprasidone
  • Aripiprazole
  • Paliperidone
  • Asenapine,
  • Iloperidone
  • Lurasidone

Aripiprazole
This is referred to as dopamine-serotonin stabilizing agent. It is a partial dopamine & 5HT1A-agonist and a 5HT2A-antagonist.
Asenapine
This has high affinity for 5-HT, dopamine, alpha & histaminergic receptors with low affinity for muscarinic receptors
Iloperidone
This acts at numerous 5-HT & dopamine receptors & has high affinity for alpha-1 receptors
Lurasidone
This is a partial 5HT1A-agonist with no affinity for muscarinic or histaminergic receptors.
Negative symptoms
Atypical antipsychotics may have increased efficacy for negative symptoms compared to typical antipsychotics
• Clozapine has demonstrated efficacy for treatment-refractory schizophrenia
• Side effects with clozapine:
• Neutropenia
• Greater risk of seizures, particularly if doses are > 600mg (some guidelinesrecommend co-prescribing of sodium valproate at such doses)
• Excessive drooling, hypotension, sedation during the early stages oftreatment, requiring slow dose increases initially.
Clozapine:
• The only antipsychotic with:
• No risk for EPS or TD
• Proven efficacy for treatment-refractory Schizophrenia
• Has been shown to reduce suicidal behaviour
• Indicated only in patients who have failed at least two previousantipsychotics – including typical & atypical antipsychotics – because of its risk of agranulocytosis
• Use requires regular monitoring of the Complete Blood Count (CBC)
• May lower seizure thresholds in patients, especially with higher doses
• use with caution in patients at risk for seizures or with a history of a seizure disorder.

Adverse Effects of Typical Antipsychotics

  • They have less EPS & hyperprolactinaemia than typical antipsychotics – Due to their higher affinity for 5HT2-receptors compared to dopamine receptors
  • Sedation – Although most associated with chlorpromazine & clozapine, it is primarily related to dosage with other antipsychotics
  • Products claiming to be less sedating can often only substantiate such claims for low doses
  • Administration of medication at bedtime often helps to minimize daytime drowsiness & may be beneficial in inducing sleep
  • Weight gain & diabetes – The atypicals are linked with weight gain, hyperlipidaemia & hyperglycaemia. A common feature of some of the newer antipsychotic drugs, especially olanzapine & clozapine
  • Anticholinergic side effects – dry mouth, constipation, blurred vision. This is particularly associated with the piperidine phenothiazines. Direct anticholinergic effect on the heart may also increase heart rate
  • Postural hypotension – α-adrenergic blockade is one of the autonomic effects of typical antipsychotics. Most pronounced adverse effect is orthostatic hypotension & as a compensatory mechanism, reflex tachycardia (the heart’s response to drop in BP). Chlorpromazine & thioridazine cause the highest degree of α-blockade
  • Blurred vision – Caused by a combination of mydriasis (dilation of the pupil) & cyclopegia (paralysis of accommodation)
  • Hormonal effects & Sexual dysfunction – These side effects are primarily influenced by the effect on prolactin
  • Galactorrhoea, gynaecomastia, missed menstrual periods, loss of libido
  • Photosensitivity – particularly associated with the aliphatic phenothiazines e.g. chlorpromazine
  • Anti-emetic effects – The antipsychotics inhibit both the chemoreceptor trigger zone & the vomiting centre
  • Neuroleptic malignant syndrome (NMS). This is rare but serious complication of antipsychotic drug treatment. Signs & symptoms of NMS include Fever, rigidity, confusion (altered mental status), diaphoresis, unstable BP, tachycardia, elevated creatine kinase (for confirmation), increased WBC count. Onset is usually sudden & should prompt immediate discontinuation of all antipsychotics. Antipsychotics are recommended not to be restarted for at least 2 weeks following the resolution of NMS. Also, it is recommended to restart antipsychotic therapy with a different medication. Treatment options: supportive care (admission to a medical ward) &withdrawal of all antipsychotic drugs – & the use of bromocriptine &/or dantrolene.

DRUG SELECTION & DOSE
• Individual Response • Selection should not be based on chemical group alone since individual response to a particular drug or dose may be more important.

Prescribing guidelines of Antipsychotics

  1. Atypical antipsychotic drugs should be considered for 1st choice for first illness patients
  2.  Atypical antipsychotic drugs should be considered for patients showing or reporting unacceptable adverse effects from typical antipsychotic drugs
  3. Patients unresponsive to two separate treatments with antipsychotic drugs, one an atypical, should be given clozapine
  4. Where more than one atypical antipsychotic drug may be suitable,the one with the lowest purchase cost should be considered
  5. Depot antipsychotic medications should be considered wherethere are grounds to suspect the patient is unlikely to take oral drugs
  6. Non-compliant patients may benefit from long-acting IM formulation of antipsychotics including:
  • Haloperidol decanoate
  • Fluphenazine decanoate
  • Long-acting risperidone
  • Paliperidone palmitate
  • Olanzapine pamoate

Drug Interactions

Phenothiazines + Tricyclic Anti-depressants (TCAs

  • Increased anti-muscarinic effects

Antipsychotics + Alcohol

  • Increased sedative effect of alcohol

Clozapine + Selective Serotonin Reuptake Inhibitors
(SSRIs)

  • Increased clozapine plasma concentration

Chlorpromazine + Propranolol

  •  Increased CPZ plasma concentration

Haloperidol/Risperidone/Olanzapine + Carbamazepine

  • Carbamazepine accelerates their metabolism

Leave a Reply

Your email address will not be published. Required fields are marked *