.jpg)
|
References:
·
Pharmacotherapy
principle and practice
·
BPAC
pharmacological management of depression in adult.
·
Ministry
of health NZ depression and management.
|
|
Definition
|
·
A serious
medical condition with a biological foundation; it responds to biological
& psychological treatments
·
Significant
and pervasive symptoms that can affect mood, thinking, physical health, work
and relationships
|
|
Signs & symptoms
|
·
Emotional: depressed mood (sadness), anhedonia (inability
to experience pleasure), pessimism, feeling of emptiness, irritability,
anxiety, feelings of worthlessness or guilt, thoughts of death/suicidal
intention
·
Physical: disturbed sleep, change in appetite/weight,
psychomotor changes, decreased energy, fatigue, bodily aches and pain
·
Cognitive: impaired concentration, indecisiveness, poor
memory
|
|
Risk factors
|
·
Parental
history of depression, difficult temperament as a child; attachment
difficulties/parental neglect
·
Family
discord; previous depression/anxiety in adulthood
|
|
Diagnosis
|
·
At least 5
depressive symptoms for at least 2 weeks: depressed mood, diminished interest
or pleasure in usual activities, ↑/↓ in appetite or weight, ↑/↓ in amount of
sleep, ↑/↓ in psychomotor activity, fatigue or loss of energy, feelings of
worthlessness or guilt, diminished ability to think, concentrate or make
decisions; recurrent thoughts of death, suicidal ideation or suicide attempt
·
SIG E CAPS -
depression, sleep, interest, guilt, energy, concentration, appetite, psychomotor,
suicide
|
|
Epidemiology
|
Cause is unknown; females are ~ twice as likely
as males to experience MDD; average age at onset is mid 20s
|
|
Pathophysiology
|
·
Biogenic
amine hypothesis: Depression may be caused
by decreased brain levels of the neurotransmitters NE, 5-HT &DA
·
Postsynaptic
changes in receptor sensitivity:
desensitization/down-regulation of NE or 5- HT1A receptors may relate
to onset of antidepressant effects
·
Dysregulation
hypothesis: failure of homeostatic
regulation of neurotransmitter systems, rather than absolute ↑/↓ in their
activities. Effective antidepressants are theorized to restore efficient
regulation to these systems
·
5-HT/NE-link
hypothesis: there is a link between
5-HT and NE activity, and that both the serotonergic and noradrenergic
systems are involved in the antidepressant response
·
The role of
DA: increased DA
neurotransmission in the mesolimbic pathway may be related to the mechanism
of action of antidepressants
|
|
Goals
|
·
To eliminate
or reduce the symptoms of depression, minimize adverse effects, ensure
compliance with the therapeutic regimen, facilitate a return to a premorbid
level of functioning.
·
Return to
euthymia; prevent relapse and suicide attempts
|
|
Pharmacological treatment
|
·
SSRI: eg: fluoxetine, paroxetine, citalopram; 1st line
for generalized anxiety disorder & for post-traumatic stress
disorder; inhibit the reuptake of serotonin -> more serotonin available in
the brain -> enhances neurotransmission, sends nerve impulses &
improves mood
o Patients should be treated for at least 12 weeks
before assessing the efficacy, may need to be continued for 6-12 months after
symptoms of anxiety have resolved
o Side effects – stomach upset, suicidal thoughts, serotonin toxicity, SIADH (low
Na), sedation, sexual dysfunction
o Interactions – SSRIS are CYP450 inhibitors -> can ↑ plasma conc of other drugs
metabolized via CYP; ↑ bleeding risk with anticoagulants & NSAIDs; ↑
serotonergic effect with St John Wort & MAOI (-> serotonin syndrome
-> avoid concomitant use); SSRIs may enhance the plasma conc &
toxicity of TCAs
o Monitor – clinical worsening, suicidality
o Patient counselling – may impair ability to drive or operate
machinery; do not stop abruptly; avoid alcohol
·
TCAs: eg: amitriptyline, clomipramine, dothiepin, imipramine, maprotilene,
mianserin, nortriptyline, trimipramine; used as 2nd line;
block reuptake of 5-HT & NA, antagonist of α1, ACh M1 & H1 receptors
o Side effects – cardiac arrhythmia, cholinergic(anti), constipation, confusion,
continence (urinary retention)
o Interactions – TCAs potentiate the effects of alcohol & other CNS depressants;
potentiate SEs of anticholinergic drugs, & the hypertensive & cardiac
effects of sympathomimetic
o Monitor – BP, blood counts, LFTs; do not start TCA or SSRI 2 weeks after
stopping MAOI
o Patient counselling – may cause drowsiness: do not operate
machinery; avoid alcohol; do not stop abruptly; may cause photosensitivity
reactions
·
MAOI: used as 3rd line; non-selective – phenelzine,
tranylcypromine; selective reversible (RIMA) – moclobemide
o Interactions – hypertensive effect with tyramine containing foods (mature cheese
-> cheese reaction; red wine, marmite, etc), levodopa, sympathomimetics;
antagonize effects of antihypertensive agents; enhance effect of
anaesthetics, antidiabetic agents, sumatriptan, opioids & nefopam,
antiepileptics, antihistamines, antipsychotics; serotonergic effect with
other antidepressants -> serotonin syndrome
o Monitoring – clinical worsening, suicidality
o Patient counselling – avoid cheese, protein extracts & other
foods/drinks with high tyramine content; limit alcohol, caffeine intake; do
not stop abruptly; may impair ability to drive/operate machinery
·
SNRI: eg: venlafaxine; 2nd line; inhibits 5-HT
& NA reuptake (greater effect on 5-HT at lower doses)
o Side effects – asthenia/fatigue, hypertension, loss of appetite, headache,
somnolence, dizziness, insomnia, nervousness, nausea, constipation, sexual
dysfunction, weakness, neck pain, diaphoresis
o Interactions – cimetidine ↑ venlafaxine conc; venlafaxine ↑ plasma conc of
antiarrhythmics, warfarin & phenothiazines; enhanced anticholinergic
toxicity with TCAs; ↑ toxicity with SSRIs & MAOIs ( serotonin syndrome)
·
NRI: eg: reboxetine; inhibits NA reuptake, weakly inhibit 5-HT
reuptake
o Side effects – insomnia, nausea, dry mouth, constipation, tachycardia, impaired
visual accommodation
o Interactions – MAOIs should not be started until 1 week after stopping NRI (risk
of acute hypertensive crises); avoid NRI 2 weeks after stopping MAOIs
o Patient counselling – may cause sleepiness: limit alcohol; do not
drive/operate machinery
·
Presynaptic α2 antagonist: (centrally acting) eg: mirtazapine; 3rd
line; blocks presynaptic α2 receptors -> ↑ in NE & 5-HT; blocks
postsynaptic 5-HT & H1 receptors
o Side effects – weight gain, dry mouth, postural hypotension, edema, drowsiness,
confusion, anxiety, insomnia, arthralgia
o Interactions – avoid concomitant use with MAOIs or within 2 weeks after stopping
MAOIs; additive serotonergic effects with other serotonergic active
substances; may ↑ sedating properties of benzodiazepines & other
sedatives; may ↑ CNS depressant effect of alcohol; cimetidine (weak inhibitor
of CYP) ↑ mirtazapine plasma conc (-> ↓ mirtazapine dose); CBZ &
phenytoin, CYP3A4 inducers ↑ its clearance (-> ↑ its dose)
|
|
Non-pharmacological
treatment
|
·
Psychotherapy – (interpersonal, cognitive & behavioral
therapy) interactive processes allow the exploration of thoughts, feelings
& behavior for the purpose of problem solving or achieving higher levels
of functioning
·
ECT (electroconvulsive therapy) – electrically-induced in patients to provide
relief from psychiatric illnesses; used as last line of intervention; monitor
BP, oxygen, HR during therapy; monitor brain waves, seizure activity &
cognitive function; ADRs – rare & short term: headache, nausea, muscle
aches
·
Bright light therapy – patients look into an into a 10000-lux
intensity light box for ~ 30/day; used for patients with SAD (seasonal
affective disorder) & as adjunctive use for MDD; ADRs – eye strain,
headache, insomnia, hypomania
|
Depression treatment plan:
|
Depression
treatment strategies:
·
Antidepressants
selection is multifactorial drug & patient characteristics and previous
response.
·
But most of the
time SSRIs are generally first line treatment for healthy adult, elderly,
small kids and breast feeding women. (see DIAGRAM 1)
·
In breast feeding,
citalopram provides lower drug exposure compared to fluoxetine
·
TCAs are relatively
safe in pregnancy. Possible link to congenital abnormalities to exposure to
paroxetine in the first trimester and perhaps other exposure outcomes with
other SSRIs.
·
Fluoxetine,
Paroxetine and mirtazapine are safe for diabetic patient.
·
SSRI are safer than
other AD in management of hypertensive patient.
·
Venlafaxine (SNRI)
is used third line after unsatisfactory response to trial of 2 other
antidepressants. Special authority is required.
·
Non-pharmacological
therapy can be considered at any stage:
Ø Psychotherapy
– (interpersonal, cognitive & behavioral therapy) interactive processes
allow the exploration of thoughts, feelings & behavior for the purpose
of problem solving or achieving higher levels of functioning
Ø ECT
(electroconvulsive therapy)
– electrically-induced in patients to provide relief from psychiatric
illnesses; used as last line of intervention; monitor BP, oxygen, HR during
therapy; monitor brain waves, seizure activity & cognitive function;
ADRs – rare & short term: headache, nausea, muscle aches
Ø Bright light
therapy – patients look into an into a
10000-lux intensity light box for ~ 30/day; used for patients with SAD
(seasonal affective disorder) & as adjunctive use for MDD; ADRs – eye
strain, headache, insomnia, hypomania
|
|
Other important monitoring, precaution, and management:
·
Monitor ADR of AD
used. Eg if SSRI used:
·
Beware of drug interaction.
(DIAGRAM 5)
Ø Eg for SSRI: CYP 450
interactions:
o
Inhibitor of CYP1A2, e.g.
fluvoxamine (strong)
o
Inhibitor of CYP2D6, e.g.
fluoxetine (strong), paroxetine (strong), sertraline (weak)
o
Inhibitor of CYP 3A4 e.g. fluvoxamine
·
Most AD can cause
orthostatic hypotension.
Ø Thus concomitant
use of antihypertensive agents can enhance the risk orthostatic hypotension
.Thus patients should be advised to lie down and raise their legs if
symptoms such as dizziness, pallor and/or sweating occur
·
When changing
antidepressants different washout periods are required depending on the
class of drug and the actual drug. (see
DIAGRAM 6
·
Evaluate treatment response
only after 4-6 weeks after the treatment started. (DIAGRAM 7)
DIAGRAM 1
DIAGRAM 2
      |
No comments:
Post a Comment