Depression and Bipolar Flashcards
How many patients, being served by a typical pharmacy serving 5000 patients, will be suffering from a mental health problem?
750.
How many patients, being served by a typical pharmacy serving 5000 patients, will suffer from mixed anxiety and depression?
300.
How many patients being served by a typical pharmacy serving 5000 patients, will suffer from depressive symptoms?
500.
How many patients, being served by a typical pharmacy serving 5000 patients, will suffer from undiagnosed depressive symptoms?
250.
How many patients, being served by a typical pharmacy serving 5000 patients, will suffer from bipolar disorder?
20
How many patients, being served by a typical pharmacy serving 5000 patients, will attempt suicide every year?
8.
How many patients, being served by a typical pharmacy serving 5000 patients, will successfully commit suicide every year?
At least once every 2 years.
What is the most common of the affective disorders?
Depression.
How can depression vary?
It varies in severity from mild (dysthymia: low grade but long term) to major depression, where delusions may occur (psychotic depression).
Define the term unipolar when it comes to affective disorder.
Low mood which alternates with normality.
Define the term bipolar when it comes to affective disorders?
Low mood which alternates with mania.
What is the prevalence of major depression?
Major depression has a lifetime prevalence of 2-4% in males and 5-9% in females.
What is the general age of onset for severe depression?
Mid to late 30s.
How long does most antidepressant therapy last for?
At least 6 months and up to 12 months after acute response to therapy.
In how many patients who recover from a single depressive episode is recurrence seen?
> 50%.
What percentage of depression cases are classified as reactive depression?
75%.
Define reactive depression.
Depression in response to external events.
What percentage of depression cases are classified as endogenous depression?
25%.
Define endogenous depression.
Depression caused by biological systems.
Do the available antidepression drugs differentiate between reactive and endogenous depression?
No.
What is the main criteria for the diagnosis of depression?
The DSM-IV Criteria for Major Depressive Disorder (MDD).
What does the DSM-IV Criteria for Major Depressive Disorder (MDD) include?
- Depressed mood or a loss of interest or pleasure in daily activities for more than two weeks.
- Mood represents a change from the person’s baseline.
- Impaired function: social, occupational, educational.
Give some depression symptoms, of which 5 or more are required for a diagnosis of depression.
- Depressed mood or irritable most of the day, nearly every day, as indicated by either subjective report. (Misery, apathy, pessimism.)
- Decreased interest or pleasure in activities. Loss of motivation – Anhedonia.
- Significant weight change (5%) or change in appetite.
- Change in sleep patterns: Insomnia or hypersomnia.
- Change in activity: Psychomotor agitation or retardation.
- Fatigue or loss of energy.
- Guilt, low self-esteem, feelings of inadequacy or worthlessness.
- Diminished ability to think or concentrate, or more indecisiveness.
- Loss of libido.
- Suicidal thoughts.
What brain region is implicated in anhedonia and reduced drive in depression?
Reward system (VTA, NAcc).
What brain region is implicated in reduced energy seen in depression?
HPA axis.
What brain region is implicated in memory problems seen in depression?
The hippocampus.
What brain regions are implicated in attention and cognitive impairment seen in depression?
The prefrontal cortex and anterior cingulate.
What brain regions are implicated in anxiety seen in depression?
The limbic system, PAG, and the amygdala.
What brain region is implicated in the immune system issues seen in depression?
HPA axis.
What is the monoamine hypothesis of depression based upon?
It was based upon the recognition that patients taking reserpine for BP control became depressed and patients taking isoniazid for tuberculosis treatment became happier.
Define the monoamine hypothesis of depression.
From this it was postulated that a lack of amines leads to depression and too many amines lead to mania.
What class of drug is reserpine?
A monoamine reuptake inhibitor.
What class of drug is isoniazid?
An MAO inhibitor.
Based on the monoamine hypothesis for depression, drugs affecting which neurotransmitters may elevate mood?
NA/5HT.
Outline some pharmacological support for the monoamine hypothesis of depression.
Inhibiting reuptake and degredation of monoamines increases their concentration in the synaptic cleft. Reserpine, which depletes monoamines, exacerbates depression.
Outline some problems with the monoamine hypothesis.
- The pharmacological effects are correlated with the blood plasma concentrations, but the therapeutic effects are delayed 3-4 weeks.
- Some effective atypical antidepressants do not modulate amine levels in the synaptic cleft.
- Cocaine potently inhibits the uptake of NADR but is not an effective antidepressant.
- Precursor amino acids increase levels of amines but are not generally effective antidepressants.
What other hypothesis about depression have been proposed?
Genetic vulnerability, Stress triggers.
Describe the genetic vulnerability seen in some patients with depression.
Polymorphisms in the 5-HT transporter and the enzyme COMT show positive correlations with depressive symptoms.
Describe the changes seen in the HPA axis when someone has depression.
- High levels of circulating cortisol.
- Elevated levels of CRH in CSF.
- Increased number of CRH-secreting neurons.
- CRH binding sites reduced in frontal cortex.
- Dysregulated circadian cortisol patterns.
- Reduced hippocampal volume.
- Increased amygdala sensitivity.
- Blockade of CRF-1 receptors reduces anxiety and depressive symptoms.
What is the dexamethasone supression test?
Cortisol levels are generally high in depressed patients and fail to respond to challenge with a synthetic steroid, dexamethasone, which, in normal patients produces a decrease in cortisol levels.
Why is mild depression generally not treated?
Because the risk-benefit ratio is poor.
What psychotherapies are used to treat mild depression?
- Cognitive behavioural therapy (CBT).
- Self-help.
- Talking therapies.
What is important to remember when starting pharmacological therapy for the treatment of depression?
That the therapeutic effects of the drug may take a while to kick in. Some patients may in fact experience a mood dip before the drugs kick in.
When may electroconvulsive therapy be used for the treatment of depression?
To treat the most severe, life-threatening depression.
What other non-pharmacological interventions may be used to treat depression?
Electroconvulsive therapy (ECT), transcranial magnetic stimulation.
What drug classes are used to treat depression?
Tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, atypicals (alpha-2-antagonists).
Give some examples of tricyclic antidepressants used to treat depression.
Amitriptyline, chlomipramine, imipramine.
Give some examples of irreversible monoamine inhibitors used for the treatment of depression.
Isocarboxazid, phenelzine, tranylcypromine.
Give some examples of reversible monoamine inhibitors used for the treatment of depression.
Moclobomide.
Give some examples of selective serotonin reuptake inhibitors used for the treatment of depression.
Citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline.
Give some examples of atypicals (alpha-2-antagonists) used to treat depression.
Mirtrazepine.
How are atypicals thought to help in the treatment of depression?
They may increase the release of amines by blocking presynaptic receptors.
What guides clinical judgement for the treatment of depression, as defined by NICE?
- Previous response to treatment.
- Tolerability of adverse effects.
- Likely side-effect profile with regard to co-morbid conditions.
- Lethality if history indicates suicide risk.
- Cost.
What class of antidepressants are used for the initial treatment of depression in adults? Why?
SSRIs. Because of better patient compliance.
What are the initial pharmacological effects of tricyclic antidepressants?
They initially inhibit amine (NA and 5-HT) reuptake increasing concentration in the synaptic cleft.
What are the later pharmacological effects of tricyclic antidepressants?
Later, further changes occur; reduction of presynaptic alpha-2 receptor sensitivity which enhances release and increased postsynaptic beta-1 receptor sensitivity which increases the efficacy of released neurotransmitters.
Which effects, the beginning effects or later effects, are the most important to the pharmacological action of tricyclic antidepressants?
The later effects.
What are the side effects of tricyclic antidepressants?
Blurred vision, dry mouth, urinary retention, constipation, excessive perspiration, postural hypotension, tachycardia, palpitations, sedation, weight gain.
What drugs do tricyclic antidepressants interact with?
Alcohol, anaesthetics, hypotensive drugs, NSAIDs.
What class of antidepressants must tricyclic antidepressants not be given with?
MAO inhibitors.
At what times the therapeutic dose are tricyclic antidepressants toxic?
10x.
Because fatalities may occur in tricyclic antidepressant overdose, how long of a treatment regimen should be given at one time?
One week.
Do MAO-B selective inhibitory drugs have an antidepressant affect?
No.
Give an example of a MAO inhibitor which is selective for MAO-A.
Moclobemide.
What are the side effects of MAO inhibitors?
Hypertensive crisis, postural hypotension, weight gain, insomnia, restlessness, convulsions.
What drugs should MAO inhibitors not be given with?
TCAs, SSRIs, or pethidine.
How do SSRIs compare to TCAs or MAOis?
They are similar in efficacy and time course to TCAs however their acute toxicity less than TCAs or MAOis.
What are SSRIs designed to target?
5-HT re-uptake.
What are the side effects of SSRIs?
Nausea, insomnia, sexual dysfunction, increases in anxiety particularly during the first phases of treatment.
What drugs, when used in combination with SSRIs, can lead to serotonin syndrome?
MAOis and MDMA.
What are the symptoms of serotonin syndrome?
Confusion, hypothermia, muscle rigidity, cardiovascular collapse.
Response to antidepressants is unlikely if the patient sees no response in how long?
4 weeks.
What can be seen if antidepressant treatment is stopped abruptly?
Discontinuation symptoms.
Continuation of antidepressant medication for how long can halve the relapse rate for depression?
> 6 months.
What are the symptoms for antidepressant withdrawal?
- Dizziness.
- Numbness and tingling.
- GI disturbances.
- Headache.
- Sweating.
- Anxiety and sleep disturbances.
In what percentage of the population does bipolar occur?
1%.
How is bipolar disorder characterised?
It is characterised by dramatic mood swings, from overtly ‘high’ to the ‘low’ of very sad and hopeless.
Define hypomania?
Hypomania is a reduced level of mania which may last for a few days.
When do bipolar symptoms typically develop?
Symptoms typically develop in late adolescence/early adult hood, with half of cases being seen below the age of 25.
Who show an increased incidence in developing bipolar? Men or women?
Women.
Does bipolar show a genetic link?
Bipolar disorder shows a strong genetic component however the specific genes are unknown.
Why may diagnosis of bipolar be difficult?
Diagnosis can be difficult since patients often enjoy the manic or hypomanic episodes so may only visit GP when depressed, also symptoms can be confused with anxiety or schizophrenia.
A questionnaire may be used to aid diagnosis of bipolar disorder, what questions might this include?
- Have you ever found yourself to be abnormally talkative and speaking very quickly?
- Have you been so manic that people thought you were not yourself?
Give the symptoms of the mania of bipolar disorder.
- Overly good, euphoric mood.
- Increased energy, activity and restlessness.
- Racing thoughts, talking fast, jumping from one idea to the next.
- Provocative, intrusive or aggressive behaviour.
- Needs little sleep.
- Unrealistic beliefs in one’s abilities and powers – delusions.
- Increased sexual drive.
- Abuse of drugs, particularly cocaine, alcohol and sleeping medications.
- A denial that anything is wrong.
Define cycling when it comes to bipolar disorder.
Cycling is the term given to the swinging of moods from lows to highs.
At what rate may cycling in bipolar occur?
There is no set rate of cycling and it can be days, weeks, or months between swings.
What are the treatment aims when it comes to bipolar disorder?
The aim of treatment is to suppress the cycling so it is maintained around normal mood.
Why shouldn’t antidepressants be given for the treatment of bipolar disorder?
One shouldn’t give antidepressants because this will push the cycling profile up to more mania.
What are the two principles in the treatment of bipolar disorder?
- Short term control of acute mania.
* Long term (prophylactic) treatment to maximise the time interval between episodes.
How is acute/overt mania controlled in bipolar disorder?
Overt mania is controlled with the neuroleptic olanzapine (NB: atypical antipsychotics not only block dopamine D2 receptors but also 5-HT2A receptors).
If carbamazepine is used for the treatment of mania in bipolar, what should be noted?
Note the greater risk of cardiotoxicity and increased propensity for drug interactions.
If sedation is a priority when treating mania in bipolar, what class of drugs should be used? Give an example.
Benzodiazepines e.g. lorazepam.
What is the most commonly used drug for prophylaxis of mania as well as depression?
Lithium carbonate.
How long does lithium carbonate have to be given for for it to build up in the system?
6 months.
What classes of drugs can be given as mood stabilising drugs?
Anticonvulsants, neuroleptics.
How long does complete lithium absorption take?
8 hours.
Give examples of anticonvulsants which may be used as mood stabilising drugs.
Carbamazepine, valporate, gabapentin.
What is the elimination half-life of lithium?
24 hours.
What are the optimum blood levels of lithium when treating bipolar disorder?
0.5-1.2 mmol/L.
At what blood concentration does severe lithium toxicity occur?
2 mmol/L.
What percentage of patients can not tolerate the adverse side effects associated with lithium?
30%.
What are the side effects of lithium used for the treatment of bipolar?
- GI discomfort and nausea.
- Neurological symptoms (which may dissipate) such as fatigue, malaise, muscle weakness.
- Decreased water reabsorption by the kidney.
- Weight gain. This is a frequent cause of non-compliance.
At moderate lithium overdose, what adverse drug effects are seen?
o Vomiting. o Abdominal pain. o Dry mouth. o Ataxia. o Dizziness. o Slurred speech. o Lethargy or excitement. o Muscle weakness.
At severe lithium overdose, what adverse drug effects are seen?
o anorexia nervosa. o persistent vomiting. o Blurred vision. o Muscle fasciculation. o Clonic limb movements. o Convulsions. o Delirium. o Syncope. o Coma. o Circulatory failure.
