Psychopharmacology for the Naturopath Flashcards
SSRI - Uses
FDA-approved
- Major Depressive Disorder
- Generalized Anxiety Disorder
- Obsessive Compulsive Disorder
- Panic Disorder
- Social Anxiety
- PMDD
- PTSD
Non-FDA-approved
- Sexual compulsions/aggression
SSRIs
- Fluoxetine (Prozac)
- Paroxetine (Paxil)
- Sertraline (Zoloft)
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Fluvoxamine (Luvox)
SSRIs - MOA
- Increase 5HT by inhibiting the function of SERT
- Increased 5HT causes 5HT1a receptors to downregulate
- Serotonergic neurons become uninhibited
SSRIs - side effects
- Sexual dysfunction
- Akathisia
- CYP450 interactions
- Hyperhydrosis
- Insomnia or sedation
- B12 depletion
- Serotonin syndrome
- Platelet dysfunction (if also taking NSAIDs)
SSRIs - CYP450 interactions
Least to Most
- Escitalopram
- Citalopram
- Sertraline
- Fluoxetine
- Fluvoxamine
- Paroxetine
SSRIs - efficacy for MDD
Best to Worst
- Escitalopram
- Citalopram
- Sertraline/fluoxetine/paroxetine
SSRIs - withdrawal syndrome
Least to Most
- Fluoxetine
- Escitalopram
- Citalopram
- Sertraline
- Paroxetine
SSRIs - activation
Least to Most
- Sertraline
- Escitalopram
- Citalopram
- Paroxetine
- Fluoxetine
SSRIs - sedation
Least to Most
- Fluoxetine/sertraline/escitalopram
- Citalopram
- Paroxetine
Fluoxetine - trade name
- Prozac
Fluoxetine
- 1st introduced SSRI
- Longest half life
> Fewest discontinuation problems, but also slowest onset of action - Activating
- Can use it to taper other drugs down
- Takes about 21 days to feel a difference
- Only SSRI FDA-approved for kids/adolescents
Paroxetine - trade name
- Paxil
Paroxetine
- Significant teratogen (only SSRI that is)
- Significant CYP interactions
- Likely to cause activation or over-sedation
- Do not use! Suggest patients switch if they’re on it
- Main good use is to decrease sexual thoughts/aggressions
- Causes a lot of side effects
- Patients might feel so fatigued that they think there’s a medical problem as well
Sertraline - trade name
- Zoloft
Sertraline
- Largest dosing window (50mg - 200mg
> Best for anxiety (use larger doses of SSRIs when treating anxiety) - Commonly causes insomnia and stomach issues (usually resolve within two weeks)
- Go-to for anxiety!
- Less activating than others
- Might cause bruxism
- Go-to for PTSD with both anxiety and MDD
Citalopram - trade name
- Celexa
Citalopram
- Often causes drowsiness
- Significant QTc prolongation
> If taking >30 mg, do regular EKGs
> More significant with co-morbidities (Hep C, diabetes, etc.) - Causes fewer other side effects
- Less sexual dysfunction than other SSRIs
Escitalopram - trade name and notes
- Lexapro
- Cleaner isomer of citalopram
- Use 1/2 the dose of escitalopram (eg. 20mg of citalopram = 10mg of escitalopram)
- Fewer side effects
- Great efficacy
- May cause bruxism
- Go-to for depression!
Fluvoxamine - trade name
- Luvox
Fluvoxamine
- Rarely seen in US
> Prescribed commonly in Europe - Only FDA approval is for OCD
Poop out syndrome
- Patient has good response to SSRI for a while (can be years), but gradually it stops working
- Can switch to a different SSRI and it will likely work
- Can discontinue the original SSRI for 6 months and then it will work again after the break
> Each subsequent use of the original SSRI will last for a shorter time before it poops out again - Happens pretty commonly
> Especially when another life stressor occurs - Tachyphylaxis is technical name for when a drug causes a great response at first, but then stops working quickly
> Poop out syndrome is only kinda-sorta the same since it’s a longer process - When true tachyphylaxis occurs with an SSRI, it’s a red flag for bipolar disorder (because they likely just need a mood stabilizer)
PTSD
- Evidence for SSRIs in PTSD is pretty poor, though SSRIs can be helpful for PTSD patients
- Significant evidence shows that SSRIs increase hippocampal volume in patients with PTSD by increasing BDNF
- Rare to see a patient with PTSD without another mood disorder, especially depression
Contraindications to SSRIs
- Past sensitivity to drug class
- Concurrent significant NSAID use (platelet dysfunction)
- History of long QTc syndrome
- Concurrent use of other QTc prolonging diagnoses or agents
- Concurrent tramadol use (for seizures)
- Bipolar disorder
Contraindications for the ND
- Hypericum
- 5HTP
- Yohimbe
- L-tryptophan
- Melatonin (may neutralize the intended enzymatic activity of the SSRI)
Depletions for the ND
- Melatonin?
> Some suggest supplementing with 1-3mg before bed
> Luvox appears to actually increase melatonin
How to stop SSRIs
- Very, very slowly
- Can replace others with very low dose Prozac to help with titration (because of its long half life)
- Can use other serotonergic support (5HTP, etc.)
- Make sure to differentiate between relapse and withdrawal symptoms
> Look for dizziness, sensitivity, suicidality
Buproprion - trade name
- Wellbutrin
Buproprion - FDA approvals
- MDD
- ADHD
- Smoking cessation
- Commonly prescribed along with SSRIs
Buproprion - formulation types
- Regular (dose TID 5 hours apart)
- Sustained Release (SR) (dose BID 3-4 hours apart morning and noonish)
- Extended Release (XL) (dose QD)
- SR often for smoking cessation and ADHD
Buproprion - MOA
- Inhibition of NE and dopamine reuptake
Buproprion - side effects
- Anxiety
- Sleep disturbance
- Jaw tightening
- Hypertension
- Lowers the seizure threshold (esp Regular and SR - must take it as prescribed)
- Can be very stimulating in the first few days, but then evens out
> Decreased sleep and appetite
Buproprion - interactions
- MAOIs
- Tramadol
> Also lowers the seizure threshold
Buproprion - contraindications
- History of seizure disorder
- History of eating disorders
> Brings back ED behaviors, even if they’ve been gone for years
SNRIs
Selective Serotonin and Norepinephrine Reuptake Inhibitors
- Venlafaxine (Effexor)
- Duloxetine (Cymbalta)
- Desvenlafaxine (Pristiq)
SNRIs - FDA approved for
- MDD
- Chronic Anxiety Disorder
- Panic Disorder
- Social Anxiety Disorder
- Chronic musculoskeletal pain**
- Fibromyalgia**
**Cymbalta only
SNRIs - MOA
- Serotonin and NE reuptake inhibition
SNRIs - side effects
Same as SSRIs
- Sexual dysfunction
- Akathisia
- CYP450 interactions (fewer than SSRIs)
- Hyperhydrosis
- Insomnia or sedation
- B12 depletion
- Serotonin syndrome
- Platelet dysfunction (if also taking NSAIDs)
- Hypertension
- Elevated hepatic enzymes
SNRIs - interactions
Same as SSRIs
- Hypericum
- 5HTP
- Yohimbe
- L-tryptophan
- Melatonin (may neutralize the intended enzymatic activity of the SSRI)
- Past sensitivity to drug class
- Concurrent significant NSAID use (platelet dysfunction)
- History of long QTc syndrome
- Concurrent use of other QTc prolonging diagnoses or agents
- Concurrent tramadol use (for seizures)
- Bipolar disorder
- Caution with L-tyrosine
SNRIs - contraindications
- Glaucoma
Venlafaxine - trade name
- Effexor
Duloxetine - trade name
- Cymbalta
Desvenlafaxine - trade name
- Pristiq
Venlafaxine
- Very bad withdrawal symptoms
> Use Prozac to taper off - Similar to Paxil in that it doesn’t get used as often anymore
Duloxetine
- Better for pain than for mood
Desvenlafaxine
- Nicer version of Effexor
- Useful for patients who haven’t had good responses to SSRIs, or patients who are drowsy/needing more energy
- Becoming cheaper and more commonly prescribed
- Commonly used for patients with a history of opiate addiction
Tricyclic antidepressants
- Amitriptyline (Elavil)
- Nortriptyline (Pamelor)
- Clomipramine (Anafranil)
- Imipramine (Tofranil)
- Doxepin (Sinequan)
TCAs - MOA
- Block serotonin transporter (SERT) and NE transporter (NET)
> Block reuptake for 5HT and NE - Increase concentrations in synaptic space
TCAs - side effects
- Prolonged QTc
- Antimuscarinic effects
> Dry mouth
> Urinary retention
> Dry eyes
> Constipation - Sexual dysfunction
- Akasthisia (rarely)
TCAs - interactions
Same as SSRIs
- Hypericum
- 5HTP
- Yohimbe
- L-tryptophan
- Melatonin (may neutralize the intended enzymatic activity of the SSRI)
- Past sensitivity to drug class
- Concurrent significant NSAID use (platelet dysfunction)
- History of long QTc syndrome
- Concurrent use of other QTc prolonging diagnoses or agents
- Concurrent tramadol use (for seizures)
- Bipolar disorder
- SAMe (accelerates the onset of action of TCAs)
- More CYP interactions than SSRIs
TCAs - contraindications
- Suicidality (TCAs are lethal at low doses)
Clomipramine
- Considered first line for OCD (then NAC, then Luvox)
> Doesn’t treat depression/anxiety as well as Luvox
> Has more side effects and CYP interactions than Luvox
Amitriptyline
- Readily used in primary care for sleep, headaches, and neuropathic pain
Nortriptyline
- Essentially the same as amitriptyline, but cleaner and more powerful
> 50mg of amitriptyline = 25mg of nortriptyline
> Fewer side effects than amitriptyline - Good for sleep
Doxepine
- Good for insomnia
Anxiolytics
- SSRIs
- Benzos
- Gabapentin
- Buspar
- Propranolol
- Clonidine
- Prazosin
SSRIs
- Start lower (1/2 usual dose)
- Go slower (wait at least 2 weeks between increasing dose)
- Go higher (will likely need the max dose to treat anxiety)
- Go-to is Zoloft
- “Max dose” is a recommendation, and some providers go higher (they just haven’t been studied at higher than “max dose”)
Benzodiazepines
- Alprazolam (Xanax)
- Lorazepam (Ativan)
- Clonazepam (Klonopin)
- Diazepam (Valium)
- Temazepam (Restoril)
Benzodiazepines - FDA approved for
- Panic disorders
- Anxiety disorders
- Insomnia
- Preoperative anxiety
- Seizures
- Muscle spasms (often used in sports medicine)
- Alcohol withdrawal
- Anything that needs the CNS suppressed…
Benzodiazepines - detox
- Prioritize detoxing patients
- Comfortable schedule for detox
> Significant patient education (decreases REM, increases anxiety, increases depression)
> Convert to Lorazepam, Valium, or Klonopin to taper (reference Ashton manual)
> Consider adding Gabapentin (300mg TID)
> 10-20% dose decrease every 2-4 weeks
> Support with GABAnergic supplements
^ Passiflora
^ Skullcap
^ GABA
^ Valerian
^ Kava
^ Phenibut
Benzodiazepines - differences
- Onset of action
- Half life
- Receptor sites
> All bind to GABA A receptors with differences within subtypes
Benzodiazepines - side effects
- Sedation
- Anxiety
- Depression
- Dizziness
- Ataxia
- Forgetfulness, feeling “fuzzy”
- “Being snowed”
- Reduced REM sleep (sleep more, but not getting rest)
Benzodiazepines - depletions
- Calcium
- Vitamin D
Benzodizepines - contraindications
- DHEA (esp Klonopin)
- CNS suppressing herbs (like Kava)
- Hypericum (CYP interactions)
Alprazolam - trade name
- Xanax
Lorazepam - trade name
- Ativan
Clonazepam - trade name
- Klonopin
Diazepam - trade name
- Valium
Temazepam - trade name
- Restoril
Benzodiazepines - general notes
- Just don’t use them if possible…
- Research says there’s no long-term reason to use them for longer than 4 weeks
- Good for patients who have bad akathisia from antipsychotics
- If discontinue abruptly, can be deadly
- Can develop tissue depletion and addictive behaviors
- Increase risk of dementia and Alzheimer’s by 60-75%
- Make EMDR less effective
- Make it more likely for patients with an acute stress response to develop PTSD (if they’re already showing PTSD symptoms)
- “Legacy” patients are ones who have been on a drug so long that it might actually be more beneficial to keep them on a low dose than to discontinue it totally
Gabapentin - trade name
- Neurontin
Gabapentin - MOA
- Neuronal calcium channel blocker
- Decreases release of glutamate
- Makes the experience of there being more GABA
Gabapentin - general notes
- Great patients who have liked CNS suppressants (benzos, opioids
- Great for easing benzo/alcohol withdrawal symptoms
- TID dosing
- Has the possibility of being abused, but much safer than benzos and opiates
Gabapentin - interactions
- Naproxen
Gabapentin - contraindications
- Few to none
- Monitor patients with poor kidney function
Gabapentin - Depletions
- B6 (when lumped in with other anticonvulsant medications…)
Buspirone - trade name
- Buspar
Buspirone - MOA
- 5-HT1A receptor partial agonist
- Minimal D4 receptor agonist
Buspirone - FDA approval
- Anxiety disorders
Buspirone - dosing
- TID
Buspirone - interactions
- Serotonergic agents and supplements
- MAOIs
- Significant CYP interactions
Buspirone - contraindications
- Bipolar disorder
Antihypertensives
- Propranolol (Inderal)
- Clonidine (Catapress)
- Prazosin (Minipress)
Antihypertensives - side effects
- Hypotension
Propranolol - trade name
- Inderal
Propranolol - MOA
- Beta blocker
Propranolol - uses
- Social anxiety/public speaking
- PTSD prevention (give in first 3 days)
- Especially indicated for patients with somatic anxiety
Propranolol - contraindications
- Diabetes mellitus (masks the s/s of hypoglycemia)
- Hypotension
- COPD
Propranolol - interactions
- Beta agonists
- Hypotensive agents
- Hawthorne
Propranolol - depletions
- CoQ10
Clonidine - trade name
- Catapress
Clonidine - MOA
- Central alpha agonist
Clonidine - uses
- Generalized anxiety with rapid thoughts
Clonidine - contraindications
- Hypotension
- Diabetes mellitus
Clonidine - interactions
- Hypotensive agents
- CNS depressants
- Hawthorne
Clonidine - depletions
- CoQ10
- B6
- B1
- Zinc
Prazosin - trade name
- Minipress
Prazosin - MOA
- Peripheral alpha blocker
Prazosin - uses
- PTSD (gold standard)
Prazosin - contraindications
- Hypotension
Prazosin - interactions
- Hypotensives
- Alpha agonists
Prazosin - depletions
- CoQ10
- Zinc
Prazosin - general note
- Slow upward titration
Second Generation Antipsychotics (SGAs)
- Clozapine (Clozaril)
- Olanzapine (Zyprexa)
- Aripiprazole (Abilify)
- Quetiapine (Seroquel)
- Risperidone (Risperdal)
- Paliperidone (Invega)
- Ziprasidone (Geodon)
- Lurasidone (Latuda)
- Asenapine (Saphris)
SGA - FDA approval
- Schizophrenia
- Schizoaffective disorder
- Acute mania
- Bipolar disorder
- Bipolar depression (Latuda, Seroquel, Abilify)
SGA - MOA
- Blocks D2 receptors in some regions of the brain
- Blocks 5HT 2A receptors
> Causes enhancement of dopamine release in certain brain regions
SGA - side effects
- Metabolic syndrome > Hyperglycemia > Hyperlipidemia > Weight gain (central) - Akathisia - Other extra-pyramidal symptoms - QTC prolongation - Sedation
SGA - metabolic concerns
Least to Most
- Lurasidone and ziprasidone
- Aripiprazole
- Asenapine
- Risperidone
- Quetiapine
- Olanzapine
SGA - side effects scale
Least to Most
- Lurasidone and ziprasidone
- Aripiprazole
- Risperidone
- Asenapine
- Quetiapine
- Olanzapine
Aripiprazole - trade name
- Abilify
Aripiprazole - notes
- “Third generation” antipsychotic
- Partial agonist of D2 receptors
- More serotonergic activity than other SGAs
- More anti-depressant effects
- Fewer metabolic and EPS SEs
- Causes problematic akathisia
- Causes gambling
- One of the most commonly used
- Often 1st line for bipolar
- Often used for adjunctive depression therapy
Olanzapine - trade name
- Zyprexa
Olanzapine - notes
- Mania sledgehammer
> Best for acute psychosis - Very sedating
- Increases CRP with just one dose
- Very popular
- Can cause 10lbs of weight gain in one week
- Can use it acutely and then transfer to a different SGA
Quetiapine - trade name
- Seroquel
Quetiapine - notes
- Very sedating
- Used for sleep issues
- Some anti-depressant effects
- Significant SEs with prolonged use
- Causes QTC prolongation
> Second to Geodon - Causes the least amount of EPS SEs
Risperidone - trade name
- Risperdal
Risperidone - notes
- Cheapest, first covered by insurance
- Medium sedation
- Minimal anti-depressant effect
- Causes prolactinemia
- Causes breast enlargement
- Becomes a 1st generation antipsychotic at 4mg
- Go-to middle-of-the-road SGA when no significant needs stand out
- In the middle for SEs and efficacy
Clozapine - trade name
- Clozaril
Clozapine - notes
- 1st SGA developed
- Not used as often anymore
- Most effective
- Causes such bad SEs that patients must be on a national registry if they’re taking it
Paliperidone - trade name
- Invega
Paliperidone - notes
- There’s an injectable version that is well-tolerated
Ziprasidone - trade name
- Geodon
Ziprasidone - notes
- IM used for psychosis
- Worst for causing QTC prolongation
Lurasidone - trade name
- Latuda
Lurasidone - notes
- Also FDA-approved for bipolar
- Currently very expensive
SGA - contraindications
- DMII (okay with monitoring)
- QTC prolongation
SGA - interactions
- Dopaminergic medications
> Ex. - Levadopa - Some CYP interactions
Mood stabilizers - general notes
- Prevent mania
- Alleviate depression (SSRIs CI in bipolar)
- Alter progression of the “disease”
- Many are anti-seizure drugs
- Some stabilize from above (tamp down mania) and some stabilize from below (lift up depression)
Mood stabilizers
- Lamictal (Lamotrigine)
- Lithium
- Depakote (Valproic acid (VPA) or Depakene)
- Tegretol
- Topomax
Lamictal - trade name
- Lamotrigine
Lamictal - MOA
- Anti-convulsant
- Blocks voltage-sensitive sodium channels
Lamictal - notes
- Best anti-depressant mood stabilizer
- Slow titration schedule to reduce allergic response/chances of developing Stevens Johnsons Syndrome
- Stabilizes from below
> Probably helps with some mania/hypomania, but more depression-oriented - Can take up to 400-800mg/day
- After 200mg, don’t get much more mood effects, but can really help with anxiety and irritability
Lamictal - side effects
- Benign rash
- Deadly rash (SJS)
- Sedation (rare)
- Blurred vision (rare)
- Stop taking immediately at first sign of a rash
Lamictal - interactions
- Depakote > Increases lamictal concentrations and risk of rash - Some oral contraceptives > Decrease lamictal concentrations - Many CYP reactions
Lamictal - contraindications and depletions
- None known
Lithium - MOA
- “unknown and complex”
- Alters sodium transport across cell membranes
Lithium - notes
- Gold standard for bipolar 1
- 3 forms: orotate, carbonate, and various “slow release” forms
- Must monitor thyroid function, kidney function, and calcium at baseline and then at least yearly
> Not true for orotate form - Stabilizes from above
- Stops suicidal ideation within a day of a minimum dose
- If dehydrated, lithium blood levels will increase (because it’s a salt)
Lithium - dosing
- 0.8-1.1 mmol/L is therapeutic range
- 0.6-0.7 mmol/L is suboptimal, but okay for maintenance
- Above 1.2 is toxic
- 0.9 is best for mania prevention
- 1.0+ has more SEs
- Can stay lower for MDD and suicidal ideation
- Must reach 0.5-0.6 for mania
Lithium - side effects
- Weight gain
- Stomach upset (switch to the long-acting form)
- Thyroid dysfunction
- Kidney dysfunction
- When reach toxicity: ataxia, delirium, tremor, nausea, vomiting (looks like serotonin syndrome)
Lithium - interactions
- Cox-2 inhibitors (like NSAIDs) > Increase lithium levels - Diuretics > Increase lithium levels - ACE inhibitors > Increase lithium levels
Lithium - contraindications
- Kidney disease
- Cardiovascular disease
- Sodium depletion
Lithium - possible positive additive effects
- Folic acid
- 5-HTP
- Inositol (watch for re-emergence of mania)
Lithium - depletions
- Chromium
Depakote - MOA
- Blocks voltage-sensitive sodium channels by an unknown mechanism
- Increases GABA by an unknown mechanism
- Anti-convulsent
Depakote - dosing
- 0.6 - 1.0 ug/mL
- Requires regular plasma
Depakote - notes
- Generally stabilizes from above
- Good for patients with a lot of anger
> Otherwise choose other meds
Depakote - interactions
- Lamictal (VPA increases lamictal plasma levels)
- Carbamazapime (VPA levels will be lowered)
- Aspirin (will increase VPA levels)
- Clonazepam (potential for rare seizures)
- CYP interactions
Depakote - contraindications
- Poor liver health > Monitor enzymes closely - Pancreatitis - Very teratogenic > Monitor anyone who has the potential of becoming pregnant
Depakote - depletions
- Folic acid
- Zinc
- Selenium
- Carnitine
- Biotin
- B12
- B1
- Copper
Sleepers
- Trazodone
- Seroquel
- Ambien
- Temazepam
Trazodone - MOA and class
- SARI (5HT agonist/reuptake inhibitor)
Trazodone - side effects
- Hangover
- Others more uncommon
> N/V
> Anticholinergic SEs
> Syncope
> EKG changes - Hangover usually doesn’t last too long, but is pretty common
Trazodone - interactions
- Many, but fairly mild
- Possibly serotonergic agents, but can be used with SSRIs
Trazodone - notes
- Go-to for falling asleep and staying asleep
- Doesn’t interrupt REM
- Aids in PTSD nightmare reduction
- No tolerance, dependence, or withdrawal
- Some people get activated if they don’t fall asleep within 30 minutes of taking it
- Possibly suppresses melatonin
Quetiapine - trade name
- Seroquel
Quetiapine - notes
- Highly sedating atypical antipsychotic
- Great for nightmares if prazosin or trazodone fail
- Must do same monitoring as all SGAs
- Causes SGA SEs
- 25-100mg for sleep
> Very histaminergic - 150-300mg for antidepressant/mood/anxiolytic
- > 400mg for antipsychosis
Zolpidem - trade name
- Ambien
Zolpidem - notes
- Almost, but not quite a benzo
> Good to just consider it one when considering prescribing it - Dependence and withdrawal
- Does not allow REM
> Harmful in PTSD - Different doses depending on biological sex
- Decreases life expectancy
- Patients report doing unsafe things while on it, or even the morning after
Temazepam - trade name
- Restoril
Temazepam - notes
- It’s a benzo
- Causes fewer euphoric effects, but more sedative effects
- Less anxiolytic than other benzos