Pharm III: L5 mental health

What should assess before prescribing antidepressants? (4)

- SI/suicide risk

- past mania/hypomania

- alcohol/drug use

- medical comorbidities

All antidepressants carry a warning of greater risk for what?

Suicide

Who is at greater risk while on antidepressants?

- patients younger than 18

- first 1-2mo of tx

Who is at high risk while on antidepressants?

patients between 18-24yo

Is there a single antidepressant that has the best efficacy?

No

What classes are 1st line for depression and chronic daily anxiety

SSRIs, SNRIs, and bupropion

SSRIs (5)

- fluoxetine

- sertraline

- paroxetine

- citalopram

- escitalopram

SSRIs MOA

- increase serotonergic activity

- decrease action of the presynaptic serotonin reuptake pump (SERT)

- increases length of time that serotonin is available in the synapse

SSRIs common early ADRs (3)

- N/D

- HA

- insomnia, activation, increased anxiety

SSRIs common ADRs (5)

- dry mouth

- sexual dysfunction

- diaphoresis/heat intolerance

- tremor (w/ higher doses)

- weight gain with long term use

SSRIs rare but serious ADRs (2)

- suicidal ideation

- mania/hypomania

SNRIs (3)

- venlafaxine

- desvenlafaxine

- duloxetine

SNRIs MOA

- block presynaptic serotonin and norepinephrine transporter proteins (SERT + NET)

- enhance postsynaptic receptor activation

SNRIs common early ADRs (4)

- N/V/HA

- insomnia/anxiety

- decreased appetite

- slight temporary weight loss

SNRIs common ADRs (6)

- dry mouth

- sexual dysfunction

- diaphroesis/heat intolerance

- tremor

- modest weight gain w/ long term

- dizziness

SNRIs rare but serious ADRs (2)

- suicidal ideation

- mania/hypomania

SNRI: which drug has an increased risk of QT prolongation?

Venlafaxine

SNRI: which drug to use for vasomotor sx of menopause

Venlafaxine

What classes are 2nd line for depression and chronic daily anxiety

TCAs, MAOIs, mirtazapine, vortioxetine

TCAs (4)

- Amitriptyline

- Doxepin

- Clopiramine

- Nortriptyline

Tricyclic (TCAs) MOA

- block reuptake of NE and 5-HT (similar to SNRIs)

- increases transmitters in synaptic cleft

- increases noradrenergic and serotonergic transmission

TCAs common ADRs (6)

- anticholinergic: constipation, urinary retention, blurred vision, dry mouth

- sexual dysfunction

- tachycardia/orthostatic hypotension

- sedation

- weight gain w/ long term use

- dizziness

TCAs rare but serious ADRs (5)

- cardiotoxic - dysrhythmias

- QTc prolongation

- suicidal ideation

- mania/hypomania

- low seizure threshold

TCAs: what to monitor in patients with cardiac risk or with higher doses?

EKG

Monoamine Oxidase Inhibitors (MAOIs) (2)

- phenelzine

- selegiline TD patch

MAOIs MOA

- inhibit MAO-A in nerve terminals

- catalyzes removal of monoamines (5-HT, histamine, DA, NE, and epinephrine)

- bond to MAO to prevent removal

- increase amount of NE, 5-HT, DA available for release

MAOIs common ADR (4)

- CNS stimulation (anxiety, insomnia, agitation, dizziness, restlessness)

- orthostatic hypotension

- sedation

- wt gain w/ long term use

MAOI interactions

Many serious drug-drug and drug-food interactions

MAOIs rare but serious ADRs (3)

- hypertensive crisis

- lethal overdose

- serotonin syndrome

MAOIs how to prevent hypertensive crisis

Low tyramine diet and avoid drug/supp that increase NE

Atypical Antidepressants (3)

- Bupropion

- Mirtazapine

- Vortioxetine

Bupropion MOA

weakly blocks reuptake at NET and DAT to increase noradrenergic and dopaminergic transmission

Bupropion ID (5)

- MDD

- prevent seasonal affective disorder

- smoking cessation

- adult ADHD

- sexual dysfunction with other antidepressants

Bupropion advantages (3)

- counteract hypoactive sexual desire caused by SSRIs

- energizing (always give in AM)

- no weight gain

Bupropion ADR (5)

- lowers seizure threshold than all antidepressants

- dry mouth, nausea

- insomnia/anxiety/agitation

- weight loss

- psychotic sx (rare)

Bupropion C/I (4)

- epilepsy

- anorexia nervosa

- bulimia nervosa

- heavy alcohol use

Mirtazapine MOA

- blockade of presynaptic a2-adrenergic receptors and histamine receptors

- increase release of 5-HT and NE

- block H1 receptors

Mirtazapine ADR (4)

- sedation (dose at night)

- drowsiness

- increased appetite

- weight gain

Vortioxetine MOA

5-HT modulator + SERT inhibition

Vortioxetine advantages (2)

- lower risk of sexual side effects

- beneficial for cognitive sx w/ depression

Vortioxetine ADR (4)

- N/V/D/constipation

- Pruritis

- HA/sedation

- dizziness, dry mouth

On antidepressants, when may patients see benefit after starting?

after 2-4 weeks

Antidepressants: Alarm symptoms (3)

- assess for mania

- assess for serotonin syndrome

- ask about SI every visit

How long should you take antidepressants to reduce relapse risk?

Minimum of 12mo

Successful antidepressant initiation

start low and go slow

How to discontinue antidepressants

- Taper over 2-4wks unless serious ADR

- for longer therapy duration, consider a longer taper off (several months)

Antidepressants: discontinuation symptoms (5)

- dizziness

- flu like sx

- insomnia

- nausea

- sensory disturbances ("brain zaps"

Antidepressants: highest risk for discontinuation due to ADE

Paroxetine and venlafaxine

Antidepressants: lowest risk for discontinuation due to ADE

Fluoxetine

Generalized Anxiety Disorder (GAD)

- Uncontrolled excessive worrying about everyday things

- more days than not for ≥6mo

Generalized Anxiety Disorder (GAD) best non drug therapy option

cognitive behavioral therapy (CBT)

GAD: 1st line (3)

SSRI/SNRI

- duloxetine

- venlafaxine

- escitalopram

GAD: 2nd line (2)

- pregabalin

- buspirone

GAD: 3rd line (2)

- TCAs

- Mirtazapine

GAD: if you need to bridge to a new medication, what drug can you use as a short term adjunct if needed?

Benzodiazepine

Buspirone MOA

- 5-HT1A partial agonist

- not a CNS depressant

Buspirone ADR (5)

- dizziness

- HA

- fatigue/sedation

- nausea

- nervousness/excitement

How should Buspirone be taken?

- must be BID or TID

- can be taken consistently with or without food

Obsessive Compulsive Disorder (OCD)

- persistent obsessions and compulsions

- recurrent, persistent thought/impulse/mental image that is unwanted and distressing

OCD 1st line

SSRI

OCD DDRI differ from panic or GAD?

needs a higher dose with a longer 8-12wk trial

OCD 2nd line

Clomipramine

Panic Disorder

- recurrent, intensely uncomfortable episodes of panic attacks

- sx reach peak in minutes and dissipate within 30min

- abrupt surge of intense fear or intense discomfort with four or more sx

Panic Disorder tx

SSRIs + CBT w/exposure

Panic Disorder: SSRI options

- fluoxetine

- paroxetine

- sertraline (FDA approved)

- venlafaxine (2nd)

Panic Disorder patients are sensitive to what?

SSRI activation

Panic Disorder: how to prevent SSRI activation

Start low, go slow, use benzodiazepine as bridge prn

Posttraumatic Stress Disorder (PTSD)

- development of anxiety after a traumatic event that elicited immediate reaction of fear, helplessness or horror

- core sx: reexperiencing event, avoiding reminders, persistent state of hyperarousal

PTSD 1st line

SSRIs/SNRIs

PTSD: which SSRIs/SNRIs are FDA approved for PTSD?

Sertraline and paroxetine

PTSD: what medication can you use to target trauma-related nightmares?

Prazosin

PTSD: what medications can you use for psychotic sx?

Add SGA such as Risperidone or Quetiapine

PTSD: what medication should you avoid if comorbid depression, substance use, and sleep issues

Benzodiazepines

Social Anxiety Disorder

- intense irrational fear of situations in which one might be scrutinized by others or may do something embarrassing or humiliating

- generalized is fear of all social situations

- performance is fear of public speaking

Generalized Social Anxiety 1st line

SSRIs/SNRIs + CBT

Performance Social Anxiety 1st line

Beta Blocker: propranolol prn 30-60min before

Performance Social Anxiety 2nd line

Benzodiazepines - Alprazolam, Lorazepam 30-60min before

Social Anxiety: what to avoid in patients with substance use risks

Benzodiazepines