Antidepressants

review key NT for CNS

-Acetylcholine (Alzheimer’s Disease)

•Role in cognition and memory

•Inactivated by acetylcholinesterase

-Dopamine (Parkinson’s Disease, Psychosis)

•Regulate motor control in basal ganglia

•Important in mood and emotion with effect on hypothalamus

-Norepinephrine and serotonin (Depression)

-GABA (Anxiety, Seizures)

which PT patients may have depression?

-Recent life changing illness/injury

-Chronic illness

-Loss of job due to illness/injury

depression: generel

-Affective disorder

-Due to decreased levels of norepinephrine and serotonin in the brain

-Disturbance in

• Amine neurotransmitters [NT]

• Serotonin, norepinephrine & dopamine

-Drug goal: increase neurotransmitter transmission

-Categories of Drugs

1) First Generation (*not much bc SE)

2) Second Generation (SSRI)

antidepressants: more effective w/ what + onset of action

-Medications are more effective with aerobic exercises

-~4-6 weeks to see effects of medication [correct medication & dose]

•Physical symptoms (ex. energy, sleep) may improve before affective symptoms

•Maximal responses can take up to 12 weeks

•Discuss with patient [don’t stop drug early]

*issue=takes awhile!

Antidepressant dosage

-Dosage: start low, slow increase

Tricyclic Antidepressants (TCA)

LAST RESORT [1^st generation]

-Amitriptyline (Elavil), Clomipramine (Anafranil

-MOA

•Thought to inhibit NE and serotonin reuptake

•Causes direct blockade of receptors for histamine, Ach & NE

•*narrow therapeutic window (*toxic easily, blood test)

-Clinical Use: Depression, neuropathic pain, fibromyalgia, post-herpetic neuralgia

-Side Effects 

•Orthostatic hypotension esp elderly

•Drowsiness, Sedation

•Significant Anticholinergic effects (xerostomia, dizziness, constipation, blurred vision, etc.)

-Adverse Effects: Cardiac toxicity—ventricular arrhythmias, QT prolongation, AV block

Monoamine Oxidase Inhibitors (MAOI)
LAST RESORT [1^st generation]

-Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline, Emsam [transdermal patch]

-MOA

•Non-selectively inhibits monoamine oxidase

•MAO inactives NTs (NE, serotonin, dopamine) 

-Clinical use: Depression

-Side Effects: Drowsiness, dizziness, HA, nausea, xerostomia

-Adverse Effects: Hypertensive crisis (MI and CVA), seizures

•CNS excitation – restlessness, irritability agitation sleep loss

•Anticholinergic effects

•Increased BP

-Serious food and drug interactions

•Tyramine food: Fermented foods and wines (Beer, Chianti wine), Some aged cheeses, Fava bean

MAO Inhibitors and Tyramine

-MAO breaks down norepinephrine and serotonin in the brain

-MAO also breaks down tyramine in the intestine

-→ stroke

Selective Serotonin Reuptake Inhibitors (SSRI)
1^st Line

*effects reuptake seretonon; have low seretonin so block reuptake

-Drugs: Fluoxetine (Prozac) Paroxetine (Paxil) Citalopram (Celexa) Escitalopram (Lexapro) Sertraline (Zoloft)

-MOA: Selectively works at synapses that use serotonin

• Block enzyme responsible for reuptake

• ↑’ed concentration of synaptic serotonin

-Clinical use: Major Depressive Disorder, General Anxiety Disorder

*+additional uses

-Side Effects d/t serotonin levels

• GI complaints: N/V/D; Insomnia; Restlessness; Headache; Sexual dysfunction

Serotonin Syndrome

Caused by overactivation of serotonin or impaired serotonin metabolism

Usually occurs 2-72 hours after Rx onset

• Mental status changes: hallucinations, agitation, coma

• Autonomic instability: tachycardia, hyperthermia, changes in BP

• Neuromuscular hyperactivity: hyperreflexia, incoordination, clonus, tremors, 

• GI disturbances: N/V/D

-Black Box Warning: may cause suicidal ideation/plans (<24 years of age)

Serotonin Norepinephrine Reuptake Inhibitors (SNRI) 1^st Line

-MOA

• Prevents reuptake of serotonin & norepinephrine not dopamine

• ↑’ed concentration

-Adverse Effects

• Serotonin syndrome (< SSRI)

Norepinephrine Dopamine Reuptake Inhibitor (NDRI)
1^st line

-MOA

•Inhibits dopamine and NE reuptake

•Does NOT act on serotonin

•↑’ed concentration of synaptic dopamine and norepinephrine

-Adverse Effects

•Increased risk of seizures due to lowering seizure threshold

Alpha 2 Antagonist  1^st Line

-Mirtazapine (Remeron)

-MOA

•Exact mechanism unknown

•Alpha-2 adrenergic receptor antagonist AND affects serotonin receptors

-Adverse Effects (*not reuptake but effects receptors)

•Serotonin syndrome

•Agranulocytosis

•Neutropenia

APTA antidepressents

Antidepressants & Chronic Pain

-Pain: neuropathic, fibromyalgia, chronic LBP

-Decreases depression from having chronic pain

-Influence monoamine transmission

•Serotonin is important in inhibition of pain

Bipolar Disorders

-Symptoms: periods of mood swings with depression and manic episodes

-Cause: imbalance in NT (serotonin, GABA, norepinephrine, dopamine, glutamate & aspartate)

Drugs:

-Prevent mood swings by preventing manic episodes, mood stabilizers or antimanic drug

-Medications [Drugs may include antipsychotics, antidepressants and anticonvulsants given in conjunction with lithium]

-Lithium

•Adverse Effects (table 7-5)

•Toxicity due to accumulation in body

•CNS - GI - CV - Renal

key takeaway biopoplar disorders

patients with bipolar disorders may be on multiple medications leading to multiplied SE

APTA bipopplar disorders

combo drugs effect cognition

*tardive dyskinsia, CV

Therapy Considerations

•Participation in treatment may be improved

•Consider need for 1 month of treatment before improvement in symptoms evident

•Side Effects can affect therapy sessions – sedation & hypotension

*pt should be able to engage; CV problems

•Adverse Effects Serotonin syndrome & Hypertensive crisis

•Onset of action - 4-6 weeks

*then particpate more

•Assess for suicidal thoughts

•Provide nonpharmacological interventions

*PT!

Therapy Implication

-Schedule therapy sessions [if possible] when drugs are effective (4-6 wks)

•Increase focus and effectiveness of learning during interventions

•If patient is sedated, therapy may not be effective [provider notification]

-Drugs are assoc. with falls in older adults

•PTs identify patients at risk, history of instability or falls, intervene with balance training, environment modifications

-PTs – promote nonpharmacological treatment by promoting exercise, massage, relaxation, yoga, sleep habits and counseling

-Assess for signs and symptoms of anxiety/depression/suicide [provider notification]

•You spend most time with patient

•Know side effects and adverse reactions

Kahoot

-all of the following medications have Serotononin Syndrome as a side effect except

-side effects/adverse reactions of Benzodiazepines include all of the following except: sedation, watery eyes, respiratory depression, psychomotor slowing

-T/F: antianxiety medicatiosn are curative

-T/F: NT GABA is primary inhibitory and Glutamate is excitatory

-norepinephrine dopamine reuptake inhibitor

-watery eyes

-False

-True