Depression Flashcards
(39 cards)
Depression
• a common mental disorder characterized by sadness, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, feelings of tiredness and poor concentration
• Children: 1 year prevalence rate of 2%
• Adolescents: 1 year prevalence rate of 4% to 8%
• National Cormorbidity Survey: 6.1%, 15-24 years
• Lifetime prevalence (up to age 18) 15%-20%
• 65% of adolescents report some depressive symptoms
• 5% to 10% of youth with subsyndromal symptoms have
considerable psychosocial impairment, high family loading
for depression, and an increased risk for suicide and
developing MDD
Signs and Symptoms
- Tiredness and loss of energy.
- Sadness that doesn’t go away.
- Loss of self-confidence and self-esteem.
- Difficulty concentrating.
- Cannot enjoy things that are usually pleasurable or interesting.
- Feeling anxious all the time.
- Avoiding other people, sometimes even your close friends.
- Feelings of helplessness and hopelessness.
- Sleeping problems - difficulties in getting off to sleep or waking up much earlier than usual.
- Very strong feelings of guilt or worthlessness.
- Finding it hard to function at work/college/school.
- Loss of appetite.
- Loss of sex drive and/or sexual problems.
- Physical aches and pains.
- Thinking about suicide and death.
- Self-harm
Emotional Symptoms
Include:
- Sadness
- Loss of interest or pleasure
- Overwhelmed
- Anxiety
- Diminished ability to think or concentrate, indecisiveness
- Excessive or inappropriate guilt
Physical Symptoms
Include:
- Vague aches and pains
- Headache
- Sleep disturbances
- Fatigue
- Back pain
- Significant change in appetite resulting in weight loss or gain
Depression: Scope of the Problem
• Mean length of episodes: 7 to 9 months • 6% to 10% become protracted • Recurrence: 30 -50% • Approximately 20% develop bipolar disorder • Associated with significant: – comorbidity – functional impairment – risk for suicide – substance use
What leads to depression?
Depression can happen suddenly as a result of physical
illness, experiences dating back to childhood,
unemployment, bereavement, family problems or other
life-changing events;
Examples of chronic illnesses linked to depression
include heart disease, back pain and cancer. Pituitary
damage, a treatable condition which frequently follows
head injuries, may also lead to depression;
Sometimes, there may be no clear reason for your
depression but, whatever the original cause, identifying
what may affect how you feel and the things that are
likely to trigger depression is an important first step.
Mild depression
a limited negative effect on your daily life. For example, you may have difficulty concentrating at work or motivating yourself to do the things you normally enjoy.
Major depression
interferes with an individual’s daily life - with eating, sleeping and other everyday activities. It can lead to hospital admission, if the person is so unwell they are at risk of harm to themselves.
Bi-polar disorder
The mood swings in bi-polar disorder can be extreme - from highs, where the individual feels extremely elated and indestructible, to lows, where they may experience complete despair, lethargy and suicidal feelings.
Post-natal depression
is more intense and lasts longer. It can leave new mothers feeling completely overwhelmed, inadequate and unable to cope. They may have problems sleeping, panic attacks or an intense fear of dying. They may also experience negative feelings towards their child.
Seasonal Affective Disorder (SAD) “winter blues”
SAD is associated with the start of winter and can last until spring when longer days bring more daylight.
Cognitive behavioural therapy (CBT)
It addresses the way you think and how this can
cause depression;
Counseling can help many depressed people
understand, accept and feel better about
themselves. People also learn more effective ways
of coping with life’s adversities and difficulties.
– Interpersonal therapy works to change how people how
to accept self and relate to others that affects mood and
self-worth.
– Cognitive therapy helps people change negative
thinking, behavior patterns and attitudes that affect self
esteem and overall sense of well being.
– It teaches you skills to identify patterns of behaviour
and thinking that are causing you problems and change
them.
Psychotherapy
Psychotherapy often looks at how past experience may be affecting your life now, so it may involve delving deeply into early experiences and key relationships; Interpersonal therapy focuses on how you relate and behave towards others. It helps you to build a better self-image and communicate more effectively with other
Drug therapy- The Monoamine Hypothesis
The Monoamine Hypothesis (1965, by Schildkraut)
• A functional deficit of the monoamine neurotransmitters,
noradrenaline, serotonin (5HT) at certain sites in the brain;
– Norepinephrine may be related to alertness and energy
as well as anxiety, attention, and interest in life;
– Serotonergic pathways in the CNS mainly involved in
mood;
– Dopamine may be related to attention, motivation,
pleasure, and reward, as well as interest in life;
There are at least two sides to the neurotransmitter story
• Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms
Drug Treatment for Depression
• Most of the antidepressant drugs target monoamine NT
turnover or monoamine receptor function;
• Little difference in efficacy between drugs predominantly on serotonergic or on noradrenergic pathways;
• Differ in their side-effect profiles;
-Tricyclic antidepressants (TCA) inhibits the reuptake of norepinephrine and serotonin;
- Serotonin specific reuptake inhibitor (SSRI) inhibits the reuptake of serotonin without affecting the reuptake of others.
- Other 5-HT/NA uptake inhibitors (SNRIs) other relatively non-selective monoamine uptake inhibitors
- Monoamine receptor antagonists block monoamine receptors
- Monoamine oxidase inhibitors (MAOIs) prevent degradation of monoamine in synapse.
- “Tricyclic” antidepressants (TCA)
• Mechanism
– inhibit monoamine reuptake, particularly the 5HT and NA, but not DA
– potency at 5HT and NA transporter varies
– similar efficacies although different affinities for NA and 5HT transporters
• Indications – depression, panic disorder
• PK
– generally well absorbed p.o. but some have significant first pass metabolism
– inter-patient differences in hepatic metabolism and Vd
(often high ~ 15 L/kg)
– variable t1/2 eg amytryptiline t1/2 =5-160 h!
– metabolites may be pharmacologically active
– dose needs to be adjusted for each patient by gradual escalation
• Caution
– depression associated with suicidal thoughts, monitoring may be necessary
– lowers threshold for seizure (epilepsy)
• Contraindication – mania
• ADR
– cardiotoxicity: Na+ channel antagonists, cardiac AV node block, tachycardia;
– also mAChR antagonist: nausea, vomiting, anorexia, dry mouth, blurred vision,
confusion, constipation, tachycardia and urinary retention.
– also may be Histamine antagonists: sedation
– also may be adrenergic antagonists: hypotension, dizziness
– may cause “serotonin syndrome” (see below)
– withdrawal over several weeks or additional ADR including panic and anxiety
• Drug interactions
– potentiate effect of CNS depression by alcohol, other cholinergic antagonists,
– drugs causing serotonin syndrome
“Tricyclic” antidepressants (TCA) examples
Amitriptyline (Elavil, etc.) Clomipramine (Novartis) Desipramine Imipramine Nortryptyline
- Selective Serotonin Reuptake Inhibitors (SSRI’s)
• Mechanism
– inhibit 5HT but not NA uptake transporters (except at high dose)
– first line treatment for depression: due to improved ADR profile compared to TCA, not cause cardiotoxicity, relatively free from mAChR, histamine and adrenergic effects seen with TCAs
– choice of drug depends on cost, ADR
– individual patient may response more favourably to one SSRI than another
• Drugs
– citalopram; fluoxetine; sertraline; paroxetine; escitalopram
• Indications
– depression, panic disorder, obsessive compulsive disorder (OCD)
• PK
– generally well absorbed p.o
– metabolites may be pharmacologically active
– long t1/2 15h-6 days
• Caution
– avoid in patients under 18 – increased risk of suicidal thoughts and efficacy unclear; fluoexetine preferred if necessary
– caution in epilepsy
• Contraindications
– Mania
• ADR
– GI effects common – nausea, constipation, diarrhoea
– increased risk of suicidal thoughts. monitoring may be necessary
– sexual dysfunction
– serotonin syndrome
– withdrawal: some SSRI’s may be addictive, withdrawal reactions common, particularly with paroxetine; specific withdrawal syndrome (GI effects, headache, anxiety, dreams, paraesthesia, “flu”, sweating); taper
off over several weeks
• Drug interactions
– may potentiate effects of MAOI
– In combination with MAOIs, SSRIs can cause serotonin syndrome
– risk of CNS toxicity with Li+ increased
- Serotonin and Noradrenalin Reuptake
Inhibitors (SNRIs)
• Mechanisms
– inhibits NA and 5-HT uptake (similar to TCAs);
– but lack major receptor-blocking actions (like SSRI)
so fewer side effects, e.g. less risk of cardiac effects;
– not currently first line therapy, rather in combination (not MAOIs)
• Drugs
– venlafaxine
» low dose is an SSRI but also blocks NA reuptake at higher dose
– duloxetine inhibits NA and 5-HT uptake
• ADR
– GI effects – especially nausea
– Hypertension
– serotonin syndrome: with other drugs affecting serotonin metabolism
• Cautions
– epilepsy – seizure threshold
– avoid hypertensive patients, MI; risk of cardiac arrhythmia
• Contraindications
– do not use with MAOIs
- Monoamine receptor antagonists
i. presynaptic a2-adrenoceptor blockers
• Mechanism – α2 adrenergic receptor antagonist » presynaptic autoreceptor inhibited – increased NAergic signalling • Drugs: -- Mirtazapine • Indications – Depression, esp. when sedation is also required as well as in elderly with insomnia/weight loss • PK – well absorbed from the gut – metabolised in the liver – long half life (20-40 h) • ADR – drowsiness – appetite stimulant – weight gain – fatigue, tremor dizziness
- Monoamine receptor antagonists
ii. serotonin receptor blockers
• Mechanism – 5HT2A, 2C antagonist • Drugs: -- Trazodone • Indications – depression • PK – well absorbed orally – metabolised in the liver – Half life 7-13h • Contraindications – avoid with MAOIs • ADR – seizure – may worsen depression in some patients
- Monoamine oxidase inhibitors (MAOIs)
i. classic (non-selective)
• Mechanism
– Non-selective, irreversible inhibition of MAO
• Drugs
– Phenelzine
– Tranylcypromine
• ADR
– Compared with TCAs, antimuscarinic effects are unusual and no predisposition to seizures;
– Dose-related postural hypotension can occur
• Drug / food interaction
– interfere with metabolism of amine-containing drugs including
» sympathomimetics – cough medicine and decongestants
» tyramine – present in several foods (e.g. aged cheeses, smoked fish)
– may cause dangerous rise in bp (warning = headache)
– specialist use only
- Monoamine oxidase inhibitors (MAOIs)
ii. Reversible inhibitor MAO-A
• Mechanism – reversible inhibitor of MAO-A • Drugs – Moclobemide • PK – oral absorption good – substantial first-pass metabolism, partially to an active metabolite – metabolised in the liver – half-life (1-2h) • ADR – Sleep disturbance, agitation, confusion – GI upset – Dizziness, headache • Drug interaction – Moclobemide should not be given with other antidepressant
