PH3113 - Psychiatric Disease and its Pharmacology 6 Flashcards
What is neuroleptic malignant syndrome (NMS)?
Its a rare life threatening side effect of antipsychotic medications
- hyperthermia
- fluctuating level of consciousness
- muscle rigidity
- autonomic dysfunction
- pallor
- tachycardia
- labile BP
- sweating
- urinary incontinence
Associated with change in dose or formulation or initiating new medication using combinations of antipsychotic medications
What is the NICE guidance on choosing anti-psychotic medications?
Decision should be made by the service user and healthcare professional together
- taking into account the views of the carer if the service user agrees
Benefits and side effects of each drug
- metabolic
- weight changes
- diabetes
- extrapyramidal
- akathisia
- dyskinesia
- dystonia
- cardiovascular
- QT interval prolongation
- hormonal
- plasma prolactin
What is the Mental Health Act (1983)?
Main piece of legislation that covers the assessment, treatment and rights of people with a mental health disorder
Give examples of affective disorders?
Major depressive disorder
- recurrent depressive episodes
Bipolar I disorder
- manic episodes and depressive episodes
Bipolar II disorder
- predominant depression
- milder manic episodes
Cyclothymia
Dysthymia
- persistent depressive disorder
What is the leading cause of disability in developed countries?
Major depressive disorder
- fourth leading cause worldwide
What is the prevalence of major depressive disorder?
Genetics and environmental factors
- 40/60
Lifetime prevalence of major depressive disorder in the US is 1 in 6 people
- 10 - 20 %
- gender difference
- more common in women
- more likely to seek help
- age on onset highly variable
- peak in men is old age
- peak in women is middle age
- direct and indirect costs are significant
- loss of productivity
- strongly associated with suicide
What are the symptoms of major depressive episode?
Low mood
Loss of interest/ pleasure from normally pleasurable activities
- anhedonia
Reduced energy
- fatigue
Low self-esteem
Feelings of guilt
Inability to think/concentrate
Altered psychomotor activity
Sleep disturbance
- early morning wakening
Altered appetite
Suicidal thoughts
How is major depressive disorder diagnosed?
2 core symptoms plus 2 or more of the minor symptoms present for most of the day and on most days for at least two weeks
What is the aetiology of major depressive disorder?
Biological
- genetic factors - polygenic
- 15% prevalence in first degree relative
- 5% in background population
- monoamine hypothesis
- alterations in the hypothalamic-pituitary axis (HPA) and immune system
Environmental/psychological
- early life adversity
- personality traits
- anxiety
- impulsivity
- obsessionality
- stressful life events
- physical illness
What is the prognosis of major depressive disorder?
Episodes tend to last for approximately 3 - 6 months
Approximately 50 - 80% of patients who have one episode of major depression will go on to have a second
- 80 - 90% of those having a second episode will have a third episode
Significant risk of suicide
- 7% in men
- 1% in women
Risk of recurrence increased by
- family history
- female gender
- social factors
- co-morbid psychiatric illness
- longer duration of episode
- co-morbid medical illness
Which hormones does the monoamine hypothesis involve?
Dopamine
- DA
Serotonin
- 5-HT
Noradrenaline
- NA
What are serotonergic and noradrenergic signalling linked with?
Mood regulation
Motivation/reward
Sleep
Pain perception
What is the process of noradrenergic signalling?
Vesicular monoamine transporter blocked by reserpine
- VMAT
Negative feedback through alpha-2 autoreceptor agonism
Noradrenaline transporter facilitates the uptake of noradrenaline
What is the process of serotonergic signalling?
Vesicular monoamine transporter blocked by reserpine
- VMAT
Negative feedback through 5HT(1A/1B) autoreceptor agonism
5-HT transporter facilitates the uptake of 5-HT
What is the monoamine theory of depression?
Many clinically effective drugs have defined neurochemical actions on monoamines in CNS
- 5-HT and noradrenaline
- firstly imipramine
- marketed as an antihistamine but prototype tricyclic anti-depressant
- iproniazid
- intended for tuberculosis but found to be an monoamine oxidase inhibitor
- anti-hypertensive reserpine induced depression
- VMAT blockade
- tryptophan depletion
- reduces 5-HT synthesis
- depressive symptoms
- increased activity in the subgenual cingulate cortex
- anti-depressants and deep brain stimulation reduce the activity of this area
- everything pointed to monoaminergic involvement in depression pathogenesis
Which brain regions are involved in depression?
Prefrontal and cingulate cortex
Hippocampus
Amygdala
Striatum
Thalamus
Neurones projecting from the locus coeruleus (NA) and raphe nuclei (5-HT) innervate all these areas
What is the definition of the monoamine theory of depression?
A pathological deficiency in serotonergic and noradrenergic neurotransmission
- need to increase monoaminergic signalling
What factors does the treatment of depression depend on?
Psychological
- cognitive behavioural therapy
- behavioural activation
- interpersonal psychotherapy
- problem solving therapy
Social
- identifying stressors
- working on strategies/signposting to other supporting organisations
Biological
- anti-depressant medication
- anti-depressants and anti-psychotic medication
- psychotic depression
