Differences between Typical and Atypical Antipsychotics: Efficacy and Adverse Effects

Typical Versus Atypical Antipsychotics

By definition, typical antipsychotics are those which produce extrapyramidal side effects, while atypical antipsychotics do not. However, at the doses used today, most atypical antipsychotics do not produce extrapyramidal side effects. Whether typical and atypical antipsychotics differ in efficacy in a long-held debate. Except for clozapine, there are no significant differences in the efficacy of typical and atypical antipsychotics. 

Two large pragmatic studies, CATIE in the United States, and CutLASS in the United Kingdom, in 2005 and 2006, respectively, produced similar conclusions. Another meta-analysis, in 2009 showed that risperidone, olanzapine, and amisulpride were more effective compared to typical antipsychotics. 

Overall, typical antipsychotics are more likely to produce extrapyramidal side effects, while atypical ones are more likely to produce metabolic side effects, including weight gain, hyperlipemia, and diabetes. 

Clozapine is more effective than both typical and other atypical antipsychotics. 

Fragile X Syndrome

Fragile X Syndrome

Fragile x syndrome is characterised by large ears, velvety skin, flat feet, testicular enlargement after puberty, speech “cluttered” attentional deficit, hand flapping.

Autistic traits. CGG repeats over two hundred.

Support –MDT. Speech and language, physio, psychological techniques for teachers/parents, look at educational needs. family support –carers' assessment.

Genetic Aberration

A mutation on the X chromosome at the Xq27.3 site. 

Fragile-X mental retardation -1 Gene

FMR1 is a human gene that codes for a protein called Fragile-X mental retardation protein (FMRP) that may help regulate synaptic plasticity, important for learning and memory. 


Prevalence

1 of every 1,000 males

1 of every 2,000 females

Intellectual disability

Mild to severe. Eighty per cent of boys with fragile X syndrome have an intelligence quotient lower than 80.

Co-morbidities

Attention deficit hyperactivity, learning disorders, autism spectrum disorders

Physical Features

long face, long ears, high, arched palate, macroorchidism, hyperextensible finger joints, flat feet.

Fragile-X Syndrome is the best answer. An elongated face is the most common physical feature. Prominent ears are also common. Macroorchidism, which refers to an increase in the size of testicles, becomes apparent at age 8 to 10 years and 80% of post-pubertal boys exhibit the feature). These hallmark features are subtle during early childhood and normally only become prominent in early adolescence.

Mitral-valve-prolapse is the most common cardiac abnormality in these patients. Seizures are also common. Septal defects occur in those with down’s syndrome. See List ‎01‑3 Manifestations of Fragile-X Syndrome for details.

An elongated face is the most common physical feature. Prominent ears are also common. Macroorchidism, which refers to an increase in the size of testicles, becomes apparent at age 8 to 10 year and 80% of post-pubertal boys exhibit the feature). These hallmark features are subtle during early childhood and normally only become prominent in early adolescence.

-       List ‎01‑3 Manifestations of Fragile-X Syndrome

Hallmark features

Elongated face

Prominent ears

Macroorchidism^[1]        

Other manifestations

High-arched palate

Flat feet

Hyperextensible joints

Behavioural Characteristics

Attention-deficit

Hyperactivity [2]

Autistic symptoms [3]

Aggressiveness

Intellectual disability [4]

Medical

Seizures [5]

Mitral prolapse

What are the physical features seen in patients with Fragile X syndrome?

Patients with Fragile X syndrome have a high rate of what co-morbidities?

Patients with Fragile X Syndrome have what severity of intellectual disability?

What is the prevalence of Fragile X Syndrome?

Describe the chromosomal aberration in Fragile X syndrome.

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[1] an increase in the size of testicles become apparent at age 8 to 10 year and 80% of post-pubertal boys exhibit the feature

[2] Most common behavioural manifestation

[3] Such as hand flapping, hand biting, perseverative speech, shyness, poor eye contact

^[4] Intellectual functioning differs in individuals with fragile-X, ranging from average intelligence to severe intellectual disability. Verbal IQ is more likely to be impaired.

^[5] Most common neurological condition

PYROMANIA

The recurrent, deliberate, and purposeful setting of fires.

Associated features

• Tension or affective arousal before setting the fires.
• Interest in fire and the actions and tools coupled with firefighting.
• Gratification, or relief setting fires or witnessing the aftermaths.

Patients make substantial advance arrangements.

Epidemiology

Eight times more frequent in men compared to women

Comorbidity

• Substance abuse disorders
• Affective disorders
• Other impulse control disorders
• Personality disturbances e.g. borderline personality disorder.
• Attention-deficit hyperactivity disorder
• Learning disabilities

History of

• Enuresis
• Antisocial acts, such as truancy and delinquency

Aetiology

Psychosocial. 

• A symbol of sexuality. 
• Abnormal craving for power and social prestige 

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• Retaliation about the absence of the father
• Volunteering as a firefighter to vent the frustration
• Promiscuity and kleptomania in females

Biological Factors. 

• Low CSF levels of 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG)
• Reactive hypoglycemia, based on blood glucose concentrations on glucose tolerance tests

Diagnosis and Clinical Features

Persons with pyromania often regularly watch fires in their neighbourhoods, frequently set off false alarms, and show interest in firefighting paraphernalia. Their curiosity is clear, but they show no remorse and may be indifferent to the consequences for life or property. Firesetters may gain satisfaction from the resulting destruction; frequently, they leave obvious clues. Commonly associated features include alcohol intoxication, sexual dysfunctions, below-average intelligence quotient (IQ), chronic personal frustration, and resentment toward authority figures. Some fire setters become sexually aroused by the fire.

Differential Diagnosis

Arson 

Firesetting for financial gain, revenge, or other motivations, prepared in advance.

Conduct disorder

Studies associate pyromania with a history of antisocial acts, such as truancy and delinquency People with antisocial personality or conduct set fire as an intentional act. They may set fires for profit or retaliation, etc.

Schizophrenia

Patients with schizophrenia or mania may set fires in response to delusions or hallucinations.

Assessment and Management of The Risk of Violence in Schizophrenia

Assessment and Management of The Risk of Violence in Schizophrenia

Scenario

A 21-year-old lady with the diagnosis of schizophrenia informs you she will kill her neighbour tomorrow as she has ruined her life. She tells not to disclose this to anyone.

1. How will you assess the homicidal risk in this patient?
2. What treatment and follow up recommendations will you make in this case?

Clinical Assessment 

Listen to the patient and develop a therapeutic relationship. 

begin the assessment and enquire about her demographics. 

Enquire about the issue that she brought up—she will kill her neighbour. 

Elaborate on how she thinks her neighbour has ruined her life. 

Explore her thoughts and whether the patient may have persecutory delusions

Assess how much resentment she feels?

Follow up with inquiry about her mood, esp. about irritability and depression

How she plans to commit the act

Has she threatened the person?

Whether she has done so in the past

If so, what provoked such an incident

Whether the provoking factor is still present

Whether she possesses a weapon.

How easily she can access her

Whether she uses alcohol or substance

Psychiatric history and mental state

Whether she has other psychotic symptoms, e.g., commanding hallucinations

Negative symptoms (reduced likelihood)

Elicit relevant personal history

Especially whether she is single, divorced or separated

Who she lives with?

Her socioeconomic circumstances

Any stressful circumstances she might be passing through

 

Tools to Assess the Risk of Violence

Buss-Durkee Hostility Inventory

•       75 (true/false)-item questionnaire

•       Used to assess cynicism and distrust

Hostility and Direction of Hostility Questionnaire

The 51-item self-report questionnaire with 5 subscales. 

Used to assess the range of manifestations of aggression, hostility, and punitiveness; distinguishes hostility as they direct it either externally (extra-punitive: psychopathic, paranoid, hysterical) or internally (internal-punitive: guilt, self-criticism)

Aggression Risk Profile

•       39-item rating scale

• Identifies the characteristics of chronically aggressive patients, to foresee future manifestations of violent behaviour

Suicide and Aggression Survey

• Semi-structured clinician-administered interview and research tool; divided into 5 parts

• Elicits a brief medical history, recent and lifetime suicidality, and tendency to social violence; measures recent and past aggressiveness expressed by suicidal acts and thoughts

Management

1. Clozapine for schizophrenia, which also reduces the risk of violence (Farooq and Taylor 2011)
2. Address the modifiable risk factors identified
3. Inform the potential victim as a precautionary measure (which is also a legal/ethical responsibility)
4. If community services are available, we should consider assertive outreach.
5. If the patient is violent, we can also consider ECT.
6. Family therapy, CBT and other psychosocial interventions for schizophrenia.