Antidepressants and Antipsychotics

What is depression?

feeling of sadness and hopelessness

-inability to experience pleasure

Is depression always apparent in people?

NO they may be able to hide it in their demeanor

What are symptoms of depression?

-change in sleep patterns

-change in appetite

-loss of energy

-suicidal thoughts

How many adults have chronic depression in US?

1.5% of adults

-half have severe depression

What percent of people with depression are being treated?

62% of people

-27% are recieving minimally adequate treatment

What are the theories to what causes depression?

-biogenic amine theory

-neurotrophic hypothesis

WHat is the biogenic amine theory?

reduction in monoamines at key sites in the brain (limbic system) causes depression

-over simplified model for depression

Waht are examples of monoamines involved in depression?

-norepinephrine

-serotonin

-dopamine

Why is biogenic amine theory thought to be over simplified?

therapeutic response with drugs that target monoamines takes multiple weeks

What structures are part of the limbic system?

-hippocampus

-frontal cortex

-cingulum

What is the neurotrophic hypothesis?

changes in trophic (growth factors) factors and hormones play a major role in development of major depression

What trophic factors are involved in the neurotophic hypothesis?

brain derived neurotrophic factors

What are neurotrophic factors?

biomolecules that support the growth, survival and differentiation of neural tissue

What is the goal of antidepressive therapy?

increase neurogenesis and synaptic connectivity in the limbic system

What is the effect of hormones on neurons?

affects the plasticity, synapse and neural networing of neural tissue

WHat is the effect of thyroid hormone on neurotrophic factors?

increases receptor sencitivity to monoamines

WHat is the effect of estrogen on neurotrophic factors?

increases receptor sencitivity to monoamines

What is the effect of cortisol on neurotrophic factors?

decreases amount of brain derived neurotrophic factors

What is the effect of testosterone on neurotrophic factors?

decreases the effectivity of neurotrophic factors

What are types of antidepressive medications?

-selective serotonin reuptake inhibitors (SSRI)

-serotonin/norepinephrine reuptake inhibitors (SNRI)

-tricyclic antidepressants (TCA)

-monoamine oxidase inhibitors (MAOI)

-atypical antidepressants

What is the effect of antidepressant drugs?

increase action of serotonin and/or norepinephrine

How do antidepressants enhance monoamines?

-block reuptake of monoamines

-inhibit enzymes that breakdown monoamines

-block receptors

What is the mechanism of action of selective serotonin reuptake inhibitors(SSRI)?

block serotonin reuptake

-increases the concentration at synaptic cleft

-significantly more selective for serotonin transporter than norepinephrine

(also shown to imapct astrocytes and BDNF levels)

What is the benefit of selective serotonin reuptake blockers?

minimal impact on other neurotransmitters means minimal side effects

What are examples of selective serotonin reuptake inhibitors(SSRI)?

-citalopram

-escitalopram

-fluoxetine

-paroxetine

-sertraline

How do selective serotonin reuptake inhibitors(SSRI) compare to other antidepressants?

-relatively safe

-minimal side effects

Why are selective serotonin reuptake inhibitors(SSRI) the drug of choice for depression?

-effective

-safe

-tolerated

-easy to use

-cost effective

How long does it take for effects of selective serotonin reuptake inhibitors(SSRI) to take effect?

2 weeks

-maximum effect in 12 weeks

What are off label uses for selective serotonin reuptake inhibitors(SSRI)?

-obsessive compulsive disorder

-panic disorders

-generalized anxiety disorder

-post traumatic stress disorder

-social axiety disorder

-premenstral dysphoric disorder

-bulimia (fluoxetine only)

Why is it important to ask what a patient takes a medication for?

because drugs can be prescribed for many different things

How are selective serotonin reuptake inhibitors(SSRI) administered?

orally

What is the effect of food on selective serotonin reuptake inhibitors(SSRI)? What is the exception?

minimal to no effect

-increases the apsorption of sertraline

What is the half life of selective serotonin reuptake inhibitors(SSRI)? What is the exception?

16 to 36 hours

-50 hours for fluoxetine (sustained release option)

What are potential side effects of selective serotonin reuptake inhibitors(SSRI)?

-HA

-sweating

-anxiety

-GI issues

-weakness

-sexual dysfunction

-weight changes (usually increase)

-sleep disturbances

What selective serotonin reuptake inhibitors(SSRI) cause sedation?

-paroxetine

-fluvoxamine

What selective serotonin reuptake inhibitors(SSRI) cause insomnia?

-fluozetine

-sertraline

What is discontinuation syndrome?

abruptly stop taking any antidepressants leading to rapid loss in serotonin levels

-as well as the down regulation of serotonin receptors

What are symptoms of discontinuation syndrome?

- flu-like symptoms

- insomnia

- nausea

- instability, dizziness

- sensory disturbances

- hyperarousal

FINISH

What feature of most selective serotonin reuptake inhibitors is going to make discontinuation syndrome so extreme?

most have a short half life

-fluoxetine will have lower risk of this

What is the mechanism of action of serotonin/norepinephrine reuptake inhibitors (SNRI)?

inhibit the reuptake of serotonin AND norepinephrine

-increase in dopamine is also seen

When are serotonin/norepinephrine reuptake inhibitors (SNRI) used?

when selective serotonin reuptake inhibitors (SSRIs) are ineffective

What are side effects of serotonin/norepinephrine reuptake inhibitors (SNRI)?

-nausea ***

-dry mouth ***

-HA

-sexual dysfunction

-dizziness

-insomnia

-fatigue

-constipation

What is the effect of low dose serotonin/norepinephrine reuptake inhibitors (SNRI)?

inhibit serotonin reuptake but minimal effect of norepinephrine

-some of the SNRIs have dosage dependent mechanism

-some of these drugs are not dose dependent and will inhibit both serotonin and norepinephrine at low doses

What is the effect of high does serotonin/norepinephrine reuptake inhibitors (SNRI)?

inhibit serotonin reuptake AND norepinephrine

-increased BP and heart rate also seen due to NE effects

What are other uses for serotonin/norepinephrine reuptake inhibitors (SNRI)?

pain disruption at level of cerebral and spinal column

-diabetic peripheral neuropathy

-post herpetic neuralgia

-fibromyalgia

-low back pain

What are examples of serotonin/norepinephrine reuptake inhibitors (SNRI)?

-desvenlafaxine

-duloxetine

-levomilnacipran

-venlafaxine

What are examples of atypical antidepressants?

-buproprion

-mirtazapine

-agomelatine

What is the mechanism of action of buproprion?

weak dopamine and norepinephrine reuptake inhibitor

What are other uses of buproprion?

-decrease cravings for nicotine withdrawal

-dry mouth

-sweating

-nervousness

-tremor

Who should not get buproprion?

patient with seizures or eating disorders

What is mechanism of action of mirtazapine?

-antagonize alpha 2 receptors (enhances norepinephrine)

-blocks various serotonin receptors (5-HR2A, 5-HT2C, 5-HT3)

-also has antihitamine activity

What are side effects of mirtazapine?

-sedating

-increased appetite

-weight gain

What is the mechanism of action of serotonin modulators?

-alter the activity of post synaptic serotonin receptors in

-inhibit reuptake of serotonin

What are examples of serotonin modulators?

-vilazodone

-trazodone

-nefazodone

-vortioxetine

What are other uses for serotonin modulators?

treat insomnia

What is the benefit of atypical and serotonin modulating antidepressants?

varying mechanismof action make them more versatile

What is the downside to atypical and serotonin modulating antidepressants?

more side effects

When are atypical and serotonin modulating antidepressants prescribed?

-when SSRIs or SNRIs are ineffective

-comorbidity makes these drugs more beneficial

What are adverse effects of atypical and serotonin modulating antidepressants?

orthostatic hypotension

What is the mechanism of action of tricyclic antidepressants?

-blocks norepinephrine and serotonin reuptake

-blocks histamine, alpha adrenergic, and muscarinic receptors

What is the main difference between tricyclic antidepressants and SNRI?

side effects

What are side effects associated with tricyclic antidepressants?

-weight gain

-dry mouth

-constipation

-blurred vision

-nausea

-drowsiness

-tachycardia/arrhythmia

What adverse effects are associated with blocking muscarinic receptors?

-blurry vision

-angle closure

-urinary retention

-tachycardia/arrhythmia

-constipation

What adverse effects are associated with blocking histamine receptors?

-sedation

-dry mouth

-dry eyes

What adverse effects are associated with blocking alph adrenergic receptors?

-orthostatic hypotension

-dizziness

-transient vision loss

What is a contraindication of tricyclic antidepressants?

narrow angles

-due to anticholenergic effects of these drugs

What are uses of tricyclic antidepressants?

-severe depression

-panic disorders

-migraine HA and chronic pain

-low dose for insomnia

What are problems with tricyclic antidepressants?

-narrow theraputic index

-drug interactions leading to toxic sedation

-exacerbate benign prostatic hyperplasia

What is the role of monoamine oxidase?

mitochondrial enzyme in nerves and gut

-safety valve to inactivate excess neurotransmitters

What is the mechanism of action of monoamine oxidase inhibitors(MAOI)?

allow nerotransmitters to escape degredation by MAO

-effective for dopamine, serotonin, and norepinephrine

What are examples of monoamine oxidase inhibitors (MAOI)?

-phenelzine

-tranylcypromine

-isocarboxazide

-selegiline

What monoamine oxidase inhibitors (MAOI) can be used transdermally?

selegiline

What are used for selegiline?

-depression

-parkinson's

What are uses of monoamine oxidase inhibitors (MAOI)?

-depression (specifically atypical depression)

-anxiety

What are adverse effects of monoamine oxidase inhibitors (MAOI)?

food and drug interactions

-other side effects are unpredictable

What is the effect of tyramine?

regulates blood pressure

What is the effect of monoamine oxidase inhibitors (MAOI) on tyramine?

severe hypertension

-MAOI can breakdown tyramine

What is serotonin syndrome?

excessive serotonin levels leading to

-high body temp

-agitation

-increased reflexes

-tremor

-sweating

-dilated pupils

-diarrhea

-seizure

-muscle breakdown

What can cause serotonin syndrome?

MAOI combined with other antidepressant

-need to make sure other antidepressant is out of system

What is mania?

opposite of depression

-enthusiasm

-anger

-rapid thought

-extreme self confidence

-impaired judgement

What is bipolar disorder?

episodes of mood swings from depression to mania

-phases can last months or weeks

-swings can affect mood, sleep, energy, judgement, behavior, and thinking

What are treatments for bipolar disorder?

-lithium

-anti-epileptic

-antipsychotic

What are adverse effects of lithium?

-downbeat nystagmus

-HA

-dry mouth

-polydipsia

-polyuria

-polyphagia

-GI distress

-hand tremors

What is psychosis?

mental disorder in which thoughts and emotions are so impaired that reality becomes distorted

What is the most common psychotic disorder?

schizophrenia

What is schizophrenia?

a psychosis characterized by delusions, hallucinations, and disturbances in speech

-associated with abnormal limbic/cortical dopaminergic neuronal pathways

What are characteristics of first generation antipsychotic drugs?

-D2 receptor antagonist

-associated with movement disorders

-anterior stellate cataracts and retinal pigment changes

-muscarinic, histaminic, and adrenergic blockade

What are characteristics of second generation antipsychotic drugs?

-D2 and serotonin receptor antagonist

-less movment disorder

-high incidents of metabolic side effects

-muscarinic, histaminic, and adrenergic blockade

What are adverse effects associate with antipsychotic drugs?

-alteration in temperature regulation

-increased pituitary prolactin release/ pituitary enlargement

What are extraparamidal signs?

-dystonia

-parkinson-like symptoms

-akathisia

-tardive dyskinesia

What is oculogyric crisis?

prolonged upward deviation of the eyes

-uncontrolled rolling back of the eyes

Which has a stronger affinity for D2 receptors: typical or atypical antipsychotic drug?

typical has higher affinity

-reason for exaggerated movements with these drugs

What is the effect of low potency first generation antipsychotics?

low potency have more movement related side effects

What can be used to treat movement disorders caused by antipsychotics?

-benztropine

What are indications that patient is using benztropine?

-near vision blur

-dilated pupils

What is tardive dyskinesia?

storage of dopamine leading to excessive movement

What is done to treat tradive dyskinesia?

vesicular monoamine transporter 2 inhibitors

-decreases dopamine levels

What are additional uses of antipsychotic drugs?

-tranquilizer

-hiccups

-autism

-tourette's

-bipolar disorders

What is neuroleptic malignant syndrome?

idiosyncratic life-threatening reaction to psych meds

-muscle rigidity, fever, altered mental status, unstable BP