Depression Flashcards
What is anxiety?
Anxiety is worrying about matters, when controlled, it can be a normal adaptive reaction.
What is depression?
Depression is a feeling of sadness and loss of interest or pleasure (not necessary after a difficult experience).
What is rumination?
When individuals retrieve and repetitively rehearse autobiographical and negatively valanced content (repetitive thinking) about past and current problems, probably one of the most problematic cognitive symptoms.
How can the scale of depression be measured?
Hamilton depression rating scale, very commonly used for clinical trial (not in primary care).
Not depressed: 0–7 Mild (subthreshold): 8–13 Moderate (mild): 14–18 Severe (moderate): 19–22 Very severe (plain): >23
There are other quick and reliable depression rating scales (more simple to use):
In primary care, use Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire (PHQ-9).
PHQ-9 may help to find undetected patient.
What happens if depression is untreated?
Takes about 6 months to recover (may be longer or become chronic).
Increase risk in morbidity and higher rates of all-cause mortality.
Increase risk of drug and alcohol addiction.
Increase risk of relapse.
Significant decline in their social and occupational functioning.
Increase risk of suicide (>x10) (2% among all depressed patients).
What is the problem of relapse?
Even if recovered, the likelihood of recurrence is high (increases with every episode).
Approximately 80% of people who receive psychiatric care for an episode of major depression have at least one more episode and a median of four episodes in a lifetime.
What should be assessed by a clinician?
Risk of suicide.
Factors which may affect the development, course and severity of depression, including:
Medical history, past history of mood elevation (e.g. determine if the depression may be part of bipolar disorder).
Living conditions and social isolation.
Availability of social support.
Learning disabilities or acquired cognitive impairments.
Identify any safeguarding concerning children or vulnerable adults in the care of someone with depression.
Comorbid conditions associated with depression: Eg alcohol, substance abuse, anxiety.
Consider using a validated measure to inform and evaluate treatment.
For mild depression: consider psychosocial an psychological intervention first (e.g. CBT).
For moderate to severe depression: consider an antidepressant and/or a high-intensity psychological intervention.
What are some factors affecting depression?
Predisposing factors:
Childhood maltreatment risk for severe, early onset, and treatment-resistant depression.
Stressful life events (e.g., job loss, psychological trauma, loss of a loved one), women more sensitive, more closely associated to cognition symptoms.
Psychiatric comorbidity (anxiety disorders, PTSD, OCD, personality, cumulative).
Physical comorbidity (pain, cardiovascular, neurological, diabetes, cumulative).
Biological risk factors (genetic vulnerability) could potentiate stress consequences, enhancing vulnerability to depression.
What animal models are used to test depressive-like symptoms and effects of antidepressant?
Sucrose preference: (gentle, test) rats giving choice between a sweet drink and tap water (if they display anhedonic behaviour they will have no preference for the sweet drink).
Tails suspension test (useful for testing antidepressant effects acutely):
Short test (a few minutes). Measurement of time to remain immobile following suspension. The quicker the animal give up the less the animal is in a fighting mood. It tests acceptance of powerlessness (defeatism) very common behaviour in depression, good for predicting antidepressant effect of a drug.
Forced swim test:
Short test. Similar principle as TST. Measurement of ability to keep swimming when introduced in a tank of water (immobility can be interpreted as a behavioral correlate of negative mood, (animal does not drown). Test responsive to antidepressants.
What treatments are used for depression?
Antidepressants:
Most of them work better than placebo, takes 3-4 weeks for significant effects. Large choice.
First-line treatment recommendations for moderate to severe major depressive disorder:
Antidepressant monotherapy, psychotherapy (CBT), and the combination of both.
Very severe depression or resistant depression:
Combination of an antidepressant and an atypical antipsychotic, electroconvulsive therapy.
Other possibilities:
Ketamine (only in hospitals and not in UK) psychedelic (in experimentation).
Children and adolescents do not respond to antidepressants the same way as adults (only fluoxetine is licensed).
Extra-care for elderly patients.
Benzodiazepines:
Very limited role; if the patient has catatonic depression, acutely suicidal depression, or depression with symptoms of anxiety, agitation, or insomnia, benzodiazepines are recommended for short term administration.
What three drugs contribute to make up the monoaminergic hypothesis of depression?
Iproniazid:
Antituberculous agent tested on patients and found to unusually elevate mood in TB patients. Further investigations show that it is also an irreversible monoamine oxidase inhibitor (inhibit degradation of monoamines). Found to have antidepressant effect on depressed patients and iproniazid analogues then put on the market (1957).
Imipramine:
(Tricyclic) discovered when looking a new antipsychotic derivatives of chlorpromazine, found to have antidepressant effects and dramatically raise serotonin levels in blood (block serotonin reuptake from platelets). In the market 1958.
Reserpine:
(Natural product) antihypertensive agent, strong monoamine depleting agent (reduce concentration of monoamine in brain), found to induce tranquilizing effect (wrongly sold as antipsychotics) but also can cause very severe depression.
Are there a monoamine deficiency in the brain of major depressed patients?
Some post mortem studies found low brain serotonin or norepinephrine levels in some areas, particularly in suicide victims (5-HT metabolite mainly).
Some studies found low metabolic levels of NA/5HT in plasma of untreated depressed patients.
Post mortem binding studies on monoamine receptors are not very consistent.
Some brain imaging studies showing increase in 5-HT transporter density in some brain areas of very severely and untreated depressed patients.
The majority of antidepressants in one way or another increase monoamine levels in brain.
Further discovery of new drugs acting more selectively on reuptake system of monoamine (some specific to serotonin, noradrenaline or mixed).
Depressed patients treated with an antidepressant in combination a monoamine synthesis inhibitor worsen.
Depressed patients in remission treated with a serotonergic antidepressant but with a diet (tryptophan depletion) causing a reduction of brain serotonin synthesis relapse.
This type of diet (tryptophan depletion) induces some mood changes in healthy volunteers (but does not worsen the untreated depressed patient.
What is the neurotrophic factor hypothesis?
Neuronal secretion and synthesis of neurotrophic factors such as BDNF (which play a role in neuronal survival, dendritic sprouting, formation of new synapses) is enhanced during antidepressant treatment and this may be controlled by monoaminergic neurotransmission.
Alternately, stress causes reduction of BDNF signalling in some part of the brain.
What is the inflammatory model?
Depression commonly occurs in illnesses associated with inflammation, such as coronary artery disease, lupus and rheumatoid arthritis.
Interferon alpha or gamma (cytokines with multiactivity) are known to cause very severe depression.
The infusion of pro-inflammatory cytokines (or inflammation inducers like the LPS) is perhaps the best experimental human model of depression,
There are evidence of altered cytokine levels during symptomatic (i.e., mania and depression) and asymptomatic intervals of the illness.
However, low grade inflammation can also be associated to many other disorders (obesity, diabetes, cvd…).
And anti-inflammatory drugs have no effect of depression or any depressive or anxiety symptoms.
How do antidepressants increase synaptic availability of serotonin or other monoamines?
Antidepressant drugs inhibit the reuptake of monoamines (such as serotonin, noradrenaline and dopamine) into the presynaptic neuron; persistence of these monoamines in the synaptic cleft results in increased postsynaptic receptor stimulation and hence in increased postsynaptic neurotransmission.
