Anti-Depressants Flashcards
Indications for antidepressants
Unipolar and bipolar depression, organic mood disorders, schizoaffective disorders, anxiety disorders, including OCD, panic, social phobia and PTSD.
How long does it take before symptoms can improve
2-4 weeks
If there is no improvement is seen after a trial of adequate length (at least 2 months) and adequate dose, what should be done
Either switch to another antidepressant or augment with another agent
If first episode of depression how long should antidepressant be continues
6mnth to year
If second episode of depression how long should antidepressant be used
2 years
Side effects of TCA’s
Antihistaminic, anticholinergic and antiadrengeric. Low blood pressure, long QT syndrome, constipation and lethal on overdose.
Tertiary TCA’s
Have tertiary amine side chains. Leads to more side effects which leads to more side effects.
Examples of teritary TCA’s
Imipramine, amitriptyline, doxepin, clomipramine
Secondary TCA’s
Metabolites of tertiary amines. These primarily block noradrenaline. The side effects are the same as tertiary but less severe.
Examples of secondary TCA’s
Desipramine, notriptyline
Monoamine Oxidase Inhibitors
These bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels. It is very effective for treatment resistant depression.
State the side effects of Monoamine Oxidase Inhibitors
orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance
Cheese reaction
Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich food or sympathomimetics
Serotonin syndrome
can develop if take MAOI with meds that increase serotonin or have sympathomimetic actions. Serotonin syndrome sx include abdominal pain, diarrhea, sweats, tachycardia, HTN, myoclonus, irritability, delirium. Can lead to hyperpyrexia, cardiovascular shock and death.
How can serotonin be avoided
need to wait 2 weeks before switching from an SSRI to an MAOI. The exception of fluoxetine where need to wait 5 weeks because of long half-life.
How do SSRI’s
These block the presynaptic serotonin reuptake
What are SSRI’s used to treat
Anxiety and depression symptoms
Side effects of SSRI’s
GI upset, sexual dysfunction (30%+!), anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness
Discontinuation syndrome from SSRI’s
Agitation, nausea, disequilibrium and dysphoria can occur if you stop the drug quickly
Examples of SSRI’s
Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Paroxetine (Paxil, Pexeva) Sertraline (Zoloft) Vilazodone (Viibryd)
Activation syndrome of SSRI’s
The drug causes increased serotonin. Can be distressing for the patient. Presents with nausea, increased anxiety, panic and agitation. This typically lasts 2-10 days.
Pros of Paroxetine
Short half life with no active metabolite means no build-up (which is good if hypomania develops) Sedating properties (dose at night) offers good initial relief from anxiety and insomnia
Cons of Paroxetine
Sedating, wt gain, more anticholinergic effects
Likely to cause a discontinuation syndrome
Pros of Sertraline
Very weak P450 interactions (only slight CYP2D6)
Short half life with lower build-up of metabolites
Less sedating when compared to paroxetine
Cons of Sertraline
Max absorption requires a full stomach
Increased number of GI adverse drug reactions
Fluoxetine Pros
Long half-life so decreased incidence of discontinuation syndromes. Good for pts with medication noncompliance issues
Initially activating so may provide increased energy
Secondary to long half life, can give one 20mg tab to taper someone off SSRI when trying to prevent SSRI Discontinuation Syndrome
Cons of Fluoxetine
Long half life and active metabolite may build up (e.g. not a good choice in patients with hepatic illness)
Significant P450 interactions so this may not be a good choice in pts already on a number of meds
Initial activation may increase anxiety and insomnia
More likely to induce mania than some of the other SSRIs
Pros of Citalopram
Low inhibition of P450 enzymes so fewer drug-drug interactions
Intermediate ½ life
Cons of Citalopram
Dose-dependent QT interval prolongation with doses of 10-30mg daily- due to this risk doses of >40mg/day not recommended!
Can be sedating (has mild antagonism at H1 histamine receptor)
GI side effects (less than sertraline)
Escitalopram pros
Low overall inhibition of P450s enzymes so fewer drug-drug interactions
Intermediate 1/2 life
More effective than Citalopram in acute response and remission
Cons of Escitalopram
Dose-dependent QT interval prolongation with doses of 10-30mg daily
Nausea, headache
Fluvoxamine pros
Shortest ½ life
Found to possess some analgesic properties
Cons of Fluvoxamine
Shortest ½ life
GI distress, headaches, sedation, weakness
Strong inhibitor of CYP1A2 and CYP2C19
Serotonin/Norepinerphrine reuptake inhibitors
Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects
How do SNRI’s treat
Depression, anxiety and possibly neuropathic pain
Pros of Venlafaxine
Minimal drug interactions and almost no P450 activity
Short half life and fast renal clearance avoids build-up (good for geriatric populations)
Cons of venlafaxine
Can cause a 10-15 mmHG dose dependent increase in diastolic BP.
May cause significant nausea, primarily with immediate-release (IR) tabs
Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration
Noted to cause QT prolongation
Sexual side effects in >30%
Duloxetine pros
Some data to suggest efficacy for the physical symptoms of depression
Thus far less BP increase as compared to venlafaxine, however this may change in time
Cons of Duloxetine
CYP2D6 and CYP1A2 inhibitor
Cannot break capsule, as active ingredient not stable within the stomach
In pooled analysis had higher drop out rate
Pros of mirtazapine
Different mechanism of action may provide a good augmentation strategy to SSRIs. Is a 5HT2 and 5HT3 receptor antagonist
Can be utilized as a hypnotic at lower doses secondary to antihistaminic effects
Cons of Mirtazapine
Increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients
Very sedating at lower doses. At doses 30mg and above it can become activating and require change of administration time to the morning.
Associated with weight gain (particularly at doses below 45mg
Buproprion Pros
Good for use as an augmenting agent
Mechanism of action likely reuptake inhibition of dopamine and norepinephrine
No weight gain, sexual side effects, sedation or cardiac interactions
Low induction of mania
Is a second line ADHD agent so consider if patient has a co-occurring diagnosis
Cons of Buproprion
May increase seizure risk at high doses (450mg+) and should avoid in patients with Traumatic Brain Injury, bulimia and anorexia.
Does not treat anxiety unlike many other antidepressants and can actually cause anxiety, agitation and insomnia
Has abuse potential because can induce psychotic sx at high doses
For a patient who has never been treated for depression before what should be used
SSRI
For patients who are treatment resistant, what can be used
Combination of antidepressants (SSRI, SNRI, mirtazepine)
Lithium
Atypical antipsychotic (quetapine, olanzapine, aripiprazole)
ECT
