NUR 3031-002 Basic Concepts of Pharm Antidepressants Lecture

Depression

The most common psychiatric disorder.

-- 300 Million people suffer worldwide

-- High risk of suicide

-- Incidence in women is twice as high as in men

-- Only 40% of people with depression saw a provider

Clinical Features of Depression

Symptoms present for most of day, nearly everyday for at least 2 weeks and include:

Depressed mood

Loss of pleasure

Insomnia (or hypersomnia)

Anorexia (or hyperphagia)

Mental slowing; loss of concentration

Feelings of guilt, worthlessness, helplessness

Thoughts of death and suicide

Overt suicidal behavior

Principles of Treatment for Depression: Lifestyle Modification

Exercise

Sleep Hygiene

Social Interactions

Principles of Treatment for Depression: Psychotherapy

Cognitive-Behavioral Therapy

Interpersonal Psychotherapy

-- Equally effective to medications in mild to moderate depression

Principles of Treatment for Depression: Pharmacotherapy

Monoamine-deficiency Hypothesis

Combination therapy (psychotherapy plus meds). --> Best for severe depression (MDD)

Principles of Treatment for Depression: Somatic Therapies

Electroconvulsive Therapy (ECT)

Transcranial Magnetic Stimulation (TMS)

-- Best for refractory depression

Depression: Principle of Pharmacotherapy (Symptoms)

Match drug choice to symptom profile

Depression Principle of Pharmacotherapy: Treatment Duration

Treatment can take several weeks to work

- Start with the lowest possible dose and increase PRN

- Switch to a different drug in the same class

- Switch to different drug in different class

- Add another drug

Depression Principle of Pharmacotherapy: Monitor SI

ALL antidepressants increase suicide risk when initiated

- Only prescribe enough to get to the next appointment

Depression Principle of Pharmacotherapy: Adherence

Instruct patients to continue taking their medications, even if symptoms lessen

-- To discontinue, patients must TAPER slowly and expect withdrawal syndrome

SSRIs: Selective Serotonin Reuptake Inhibitors MOA

Blocks reuptake of serotonin (5HT) in the synapse, leaving excess serotonin to attach to receptors

-- CNS Excitation

SSRIs: DON'T DO?

- Do NOT block reuptake of dopamine or norepinephrine

- Do NOT block cholinergic, histaminergic, or alpha-adrenergic receptors

SSRIs: Examples

Fluoxetine (Prozac)

Sertraline (Zoloft)

Paroxetine (Paxil)

SSRIs: Adverse Effects

Nausea, Headache,

CNS Stimulation: Insomnia, nervous/anxiety

Better to take in the morning

Why are SSRIs typically prescribed?

Best for patients with: Hypersomnolence (oversleeping)

Better to take in the morning

SSRIs Adverse Effects: Withdrawal Syndrome

Starts within days of discontinuation

-- Can last 1-3 Weeks

-- MUST Taper SLOWLY

SSRIs: Withdrawal Syndrome S/S

SSRI Withdrawal:

Dizziness, headache, nausea, anxiety, tremor, dysphoria

SSRIs Adverse Effects: Sexual Dysfunction

Reason for occurrence is unknown

- Decreased Libido

- Impotence

- Delayed or absent orgasm

- Delayed or absent ejaculation

SSRIs Adverse Effects: Sexual Dysfunction (Patient Education)

Instruct patients to inform the provider.

- Clients can try a "Drug Holiday" --> hold the drug on Friday/Saturday

-- Add another drug (Wellbutrin, Buspar, Viagra)

SSRIs Adverse Effects: Weight Gain

Short term: weight loss

Long term: weight gain (1/3 patients)

Good for patients with loss of appetite and weight loss

SSRIs Adverse Effects: Serotonin Syndrome

2-72 hours after treatment onset

S/S: Altered mental status (confusion, agitation, hallucinations), Myoclonus, Hyperreflexia, sweating tremor, fever

SSRIs Adverse Effects: GI and Fluid Imbalance

SSRIs can cause GI bleeds: use cautiously with blood thinners and antiplatelet agents

- SSRIs can also cause HYPOnatremia

SSRI Use in Pregnancy

Late pregnancy can cause abstinence syndrome and pulmonary hypertension in newborns

- Septal Heart Defects: low risk, not well established for all SSRIs

SSRIs Drug Interactions (MAOIs)

High risk of serotonin syndrome

-- MUST wait at least 2 weeks between discontinuation of one and introducing another

SSRIs Drug Interactions (Prozac)

Wait 5 weeks before starting MAOI due to the long half-life

SNRIs: Serotonin/Norepinephrine Reuptake Inhibitors

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

SNRIs: Serotonin/Norepinephrine Reuptake Inhibitors MOA

Blocks the reuptake of serotonin and norepinephrine

- Weak blockade of dopamine reuptake

- CNS excitation

What do SNRIs NOT Do?

SNRIs do NOT block cholinergic, histaminergic, or alpha-adrenergic receptors

Why may SNRIs also be used?

Also used for pain;

Fibromyalgia

Diabetic Neuropathy

SNRIs Adverse Effects:

Adverse Effects of SNRI:

• Diastolic Hypertension

• Serotonin Syndrome

• Hyponatremia

• CNS Stimulation (insomnia/anxiety)

• Withdrawal Syndrome

Why are SNRIs better for patients who overeat, have pre-existing obesity, or experience weight gain?

An adverse effect of SNRIs includes Anorexia and Weight LOSS.

Tricyclic Antidepressants (TCAs)

Amitriptyline (Elavil)

Tricyclic Antidepressants (TCAs) MOA

Blocks reuptake of norepinephrine, some block reuptake of serotonin.,

- Blocks receptors for histamine, acetylcholine, and Alpha-1

TCAs Adverse Effects Suicidality:

Suicidality: Overdose of TCAs

- (only prescribe a 1-week supply; must keep appointments to receive refills)

TCAs Adverse Effects: Sedation

Histamine blockade

- (good option for patients with insomnia) (take at night)

TCAs Adverse Effects: Orthostatic Hypertension

Alpha Blockade

- (Instruct patients to move slowly when changing position; sit or lie down if dizziness occurs)

TCAs Adverse Effects: Anticholinergic Effects

Acetylcholine Blockade

- (dry mouth, blurred vision, constipation, urinary hesitation, tachycardia)

TCAs Adverse Effects: Cardiac Toxicity

ECG Before and periodically during treatment.

TCAs Adverse Effects: Seizures

Lowers seizure threshold; use cautiously in people with seizure disorders.

MAOIs: Monoamine Oxidase Inhibitors MOA

Inhibits monoamine oxidase,

preventing breakdown of amine

neurotransmitters, leaving more available in

the synapse

Monoamine Oxidase

Found in Liver and Intestinal Wall:

Inactivates tyramine and other amines in food/drugs

Terminals of Monoamine-containing Neurons

Convert monoamine neurotransmitters into inactive products.

- Norepinephrine - MAO-A

- Serotonin - MAO-A

- Dopamine - MAO-B

MAOIs Wash Out Period:

Discontinuation of MAOI --> takes the body 2 weeks to manufacture enough new monoamine oxidase.

-- Must wait 2 weeks to start a new antidepressant

Examples of MAOIs

• Isocarboxazid

• Phenelzine (Nardil)

• Selegiline (transdermal)

MAOIs Adverse Effects:

Adverse Effects of an MAOI:

CNS Stimulation: Hypomania/MANIA, Insomnia, anxiety, agitation

Orthostatic hypotension

MAOIs Hypertensive Crisis

AVOID TYRAMINE-RICH FOODS

Tyramine is usually inactivated in the intestine and liver through the first-pass effect

--> With MAOI's, enters systemic circulation intact

• Tyramine stimulates release of

norepinephrine in the peripheral

sympathetic nerves, causing massive

vasoconstriction and cardiac stimulation

S/S of MAOI Hypertensive Crisis

S/S of MAOI Hypertensive Crisis

• Headache

• Tachycardia

• Palpitations

• Nausea/vomiting

• Hypertension

• Confusion

• Diaphoresis (sweating)

MAOI Patient Education:

• Avoid all medications not prescribed/approved by provider

• Avoid foods rich in tyramine, caffeine, and phenylethylamine

MAOI: Patient education of Food HIGH in Tyramine

• Cheese

• Fermented, smoked, cured, or aged fish or meat

• Foods with yeast: beer, baked goods made with yeast

• Figs, avocados, bananas

• Fermented soy or bean curd

• Chocolate (caffeine & phenylethylamine)

• Caffeinated beverages (coffee, tea, soda)

Atypical Antidepressants: Bupropion (Wellbutrin) MOA

Unclear, may block dopamine or NE uptake.

Common Side Effects: -->

Appetite suppression

Increased libido and sexual pleasure

Seizures

Anticholinergic effects

Atypical Depressants: Mirtazapine (Remeron) MOA

Blocks alpha2 increasing release of serotonin and NE

- (blocks serotonin subtype receptors)

- (blocks histamine receptors)

- (mild muscarinic blockade)

Atypical Depressants: Mirtazapine (Remeron) Side Effects

Mirtazapine (Remeron) SE:

Sedation - avoid alcohol

Weight gain

Anticholinergic Effects (mild)