Anti-Depressants

Question 1

Indications for antidepressants

Answer 1

Unipolar and bipolar depression, organic mood disorders, schizoaffective disorders, anxiety disorders, including OCD, panic, social phobia and PTSD.

Question 2

How long does it take before symptoms can improve

Answer 2

2-4 weeks

Question 3

If there is no improvement is seen after a trial of adequate length (at least 2 months) and adequate dose, what should be done

Answer 3

Either switch to another antidepressant or augment with another agent

Question 4

If first episode of depression how long should antidepressant be continues

Answer 4

6mnth to year

Question 5

If second episode of depression how long should antidepressant be used

Answer 5

2 years

Question 6

Side effects of TCA’s

Answer 6

Antihistaminic, anticholinergic and antiadrengeric. Low blood pressure, long QT syndrome, constipation and lethal on overdose.

Question 7

Tertiary TCA’s

Answer 7

Have tertiary amine side chains. Leads to more side effects which leads to more side effects.

Question 8

Examples of teritary TCA’s

Answer 8

Imipramine, amitriptyline, doxepin, clomipramine

Question 9

Secondary TCA’s

Answer 9

Metabolites of tertiary amines. These primarily block noradrenaline. The side effects are the same as tertiary but less severe.

Question 10

Examples of secondary TCA’s

Answer 10

Desipramine, notriptyline

Question 11

Monoamine Oxidase Inhibitors

Answer 11

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.

Question 12

State the side effects of Monoamine Oxidase Inhibitors

Answer 12

orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance

Question 13

Cheese reaction

Answer 13

Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich food or sympathomimetics

Question 14

Serotonin syndrome

Answer 14

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.

Question 15

How can serotonin be avoided

Answer 15

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.

Question 16

How do SSRI’s

Answer 16

These block the presynaptic serotonin reuptake

Question 17

What are SSRI’s used to treat

Answer 17

Anxiety and depression symptoms

Question 18

Side effects of SSRI’s

Answer 18

GI upset, sexual dysfunction (30%+!), anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness

Question 19

Discontinuation syndrome from SSRI’s

Answer 19

Agitation, nausea, disequilibrium and dysphoria can occur if you stop the drug quickly

Question 20

Examples of SSRI’s

Answer 20

Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Paroxetine (Paxil, Pexeva)
Sertraline (Zoloft)
Vilazodone (Viibryd)

Question 21

Activation syndrome of SSRI’s

Answer 21

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.

Question 22

Pros of Paroxetine

Answer 22

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

Question 23

Cons of Paroxetine

Answer 23

Sedating, wt gain, more anticholinergic effects

Likely to cause a discontinuation syndrome

Question 24

Pros of Sertraline

Answer 24

Very weak P450 interactions (only slight CYP2D6)
Short half life with lower build-up of metabolites
Less sedating when compared to paroxetine

Question 25

Cons of Sertraline

Answer 25

Max absorption requires a full stomach | Increased number of GI adverse drug reactions

Question 26

Fluoxetine Pros

Answer 26

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

Question 27

Cons of Fluoxetine

Answer 27

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

Question 28

Pros of Citalopram

Answer 28

Low inhibition of P450 enzymes so fewer drug-drug interactions Intermediate ½ life

Question 29

Cons of Citalopram

Answer 29

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)

Question 30

Escitalopram pros

Answer 30

Low overall inhibition of P450s enzymes so fewer drug-drug interactions Intermediate 1/2 life More effective than Citalopram in acute response and remission

Question 31

Cons of Escitalopram

Answer 31

Dose-dependent QT interval prolongation with doses of 10-30mg daily Nausea, headache

Question 32

Fluvoxamine pros

Answer 32

Shortest ½ life | Found to possess some analgesic properties

Question 33

Cons of Fluvoxamine

Answer 33

Shortest ½ life GI distress, headaches, sedation, weakness Strong inhibitor of CYP1A2 and CYP2C19

Question 34

Serotonin/Norepinerphrine reuptake inhibitors

Answer 34

Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects

Question 35

How do SNRI's treat

Answer 35

Depression, anxiety and possibly neuropathic pain

Question 36

Pros of Venlafaxine

Answer 36

Minimal drug interactions and almost no P450 activity | Short half life and fast renal clearance avoids build-up (good for geriatric populations)

Question 37

Cons of venlafaxine

Answer 37

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%

Question 38

Duloxetine pros

Answer 38

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

Question 39

Cons of Duloxetine

Answer 39

CYP2D6 and CYP1A2 inhibitor Cannot break capsule, as active ingredient not stable within the stomach In pooled analysis had higher drop out rate

Question 40

Pros of mirtazapine

Answer 40

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

Question 41

Cons of Mirtazapine

Answer 41

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

Question 42

Buproprion Pros

Answer 42

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

Question 43

Cons of Buproprion

Answer 43

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

Question 44

For a patient who has never been treated for depression before what should be used

Answer 44

SSRI

Question 45

For patients who are treatment resistant, what can be used

Answer 45

Combination of antidepressants (SSRI, SNRI, mirtazepine) Lithium Atypical antipsychotic (quetapine, olanzapine, aripiprazole) ECT