Digital PharmD

Informatics in Pharmacy

Psychiatry

Substance Abuse Disorders

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Alcohol Withdrawal –

  • Tremors start around 6 hours, seizures around 12 hours, but can occur 3-5 days later.
  • Mortality can be as high as 35%.
  • 3 Ts – Increase temp, tremor and tachycardia
  • Treatment: correct electrolyte imbalances, benzos, can use propofol or barbiturates in refractory cases, magnesium, alpha 2 agonists, Beta blockers, calcium channel blockers
  • Avoid: tramadol, meperidine, Thorazine, bupropion, TCAs, fluoroquinolones, carbapenems, theophylline, romazicon (huge risk of seizure in chronic user)
  • Use Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar): 0-67, higher is worse. Treat if 8-10.
  • Benzos are main treatment:
    • Lorazepam: 2-4 mg every 6 hours (preferred, no active metabolites, no liver interactions)
    • Diazepam: 10-20 mg every 5 hours (lower in liver failure)
    • Chlordiazepoxide: 50-100 mg every 6 hours (long-acting, decrease dose in liver issues
  • Thiamine: prevent Wernicke-Korsakoff syndrome
  • Magnesium: Check labs to see if needed
  • Electrolyte labs, such as potassium
  • Vitamins: Patients are usually undernourished
  • Fluid therapy: patients are initially overhydrated, then dehydrated, usually give 5% dextrose
  • Hallucinations can be controlled by BZDs or haloperidol
  • Beta-blockers: can control tremor, heart rate and blood pressure
  • Alpha-agonist: clonidine can help with withdrawal
  • Can use disulfiram, naltrexone, acamprosate for chronic therapy.  All are liver toxic.  Naltrexone is better in liver dysfunction.

Opioid Dependence –

  • Maintenance with methadone, naltrexone, buprenorphine.  Opioid withdrawal is not fatal (flu-like symptoms).  Methadone must be tapered to 30 mg daily or less before discontinued.

Tobacco –

  • 10+ cigarettes a day = 21 mg patch, decrease in 2 weeks
  • <10 cigarettes a day = 14 mg patch, decrease in 6 weeks
  • Gum: max = 24 pieces a day, use at least 9 pieces per day.  > 24 cigarettes a day = 4mg gum, all others use 2 mg gum
  • Lozenges – people who smoke within 30 minutes of waking use 4 mg, all others use 2 mg.
  • Bupropion – start at least 7 days before quitting.  Treat at least 8 weeks, up to 6 months.
  • Varenicline: start 7 days prior to quitting, use at least 12 weeks (can use up to 24 weeks).  Black box warning for psychosis.  Can be combined with bupropion or a patch.

Sleep Disturbances

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Lifestyle Modifications:

  • Maintain sleep schedule
  • Do not go to bed unless tired
  • Sleep long enough, but not too much
  • Optimize bedroom lighting, temp and sound
  • Develop a ritual
  • Do not stay in bed for more than 15 minutes if you can’t sleep
  • Don’t go to bed hungry.
  • Only use the bedroom for sleep
  • Avoid naps
  • Avoid stimulants
  • Avoid alcohol
  • Exercise regularly, but not close to bedtime.

BZDs used for sleep are effective and generally well tolerated. Not considered first line because of potential of dependance, decreased REM, risk of angioedema and psychosis.

BenzodiazepineOnset of ActionPeak OnsetHalf-life parent (hrs)Half-life metabolite (hrs)Comparative Oral Dose
Long Acting
FlurazepamRapid0.5-2inactive47-10030 mg
Intermediate  Acting
 TemazepamSlow 0.75-1.510-20– 30mg
Short Acting
TriazolamInt.0.75-21.6-5.5–0.5mg

Sleep aids:

MedicationSleep onsetSleep maintenanceCyp interactionsNotes
ramelteon (Rozerem)X  Melatonin agonist, hepatic concerns
Do not use with fluvoxamine
tasimelteon (Hetlioz)   Also for non-24, melatonin agonist
eszopiclone (Lunesta)X 3A4 substrateGaba agonist, Decrease dose with 3A4 inhibitors
zaleplon (Sonata)X  Gaba agonist
zolpidem (Ambien)X 3A4 substrateGaba agonist
Decrease dose in women, with 3A4 inhibitors
in older patients
-zolpidem (Edular SL tablet)X 3A4 substrate 
-zolpidem (Zolpmist SL spray)X 3A4 substrate 
-zolpidem (Ambien XR)X 3A4 substrateMust have 4-8 hours of planned sleep.
-zolpidem (Intermezzo SL tablet) X3A4 substrate 
doxepin (Silenor) X Especially good for elderly or depressed.
Do not give with MAOIs
melatoninX  Especially good for elderly.
suvorexant (Belsoma)X 3A4 / 2C9Decrease digoxin dose.
mirtazapine   Good in depression.
     
  • Depressed patients: mirtazapine, dozepin +/- trazodone
  • Older patients: doxepin, melatonin, ramelteon

Here’s a chart I copied with adverse effects of various sleeping aids, but I didn’t write down where it was from.

Depression

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Diagnosis:

MDD – Major Depressive Disorder/Unipolar Disorder
At least five symptoms every day for at least 2 weeks.
Depressed mood = SIG E CAPS

  • Sleep disturbances
  • Interest in activities lost
  • Guilt or worthlessness feelings
  • Energy decreased
  • Concentration decreased
  • Appetite and weight changes
  • Psychomotor retardation
  • Suicidal ideation

Rating Scales:

  • HAM-D: Hamilton rating scale for depression – 18 moderate, 7 normal
  • CGT: Clinical Global Impression Scale
  • MADRS: Montgomery-Asberg Depression Rating Scale
  • PHQ-9: Patient Health Questionnaire
  • Beck Depression Inventory
  • Quick Inventory of Depressive Symptoms (self-rated)

Treatment:

  • Psychotherapy may have longer-lasting effects than drugs, but it takes longer to take effect.
  • All anti-depressants are equally as effective, but take 1-2 weeks for effect and 6-8 weeks for full effect.  Treat for at least 6 months.  An adequate trial is considered to be 4-8 weeks.  Look for at least a 50% decrease in symptoms.
  • SSRIs are the cheapest and most tolerated drug class: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vilazodone.  SNRIs are very similar, but also decrease seizure threshold: venlafaxine, desvenlafaxine, duloxetine, nefazodone, levomilnacipran
    • AE: diarrhea (especially sertraline), drowsiness (fluvoxamine and paroxetine are most sedating, fluoxetine and sertraline are most activating), anxiety, sexual disorder, serotonin syndrome (especially when combined with meperidine, tramadol, MAOI or linezolid), SIADH (especially in elderly), pulmonary HTN (especially paroxetine), weight gain (citalopram, escitalopram and fluoxetine are the most weight neutral)
    • Least likely for drug interactions: citalopram and escitalopram, fluoxetine and paroxetine.
    • Fluoxetine has the slowest onset and the longest half-life.
    • Duloxetine has an indication for diabetic neuropathy
    • Limit dose of citalopram to 40 mg due to QT prolongation
    • Fluoxetine 90 mg can be taken once weekly
    • Venlafaxine is known to cause withdrawal problems
    • Symptoms of serotonin withdrawal: dizziness, lightheadedness, feeling faint, shock-like sensations, anxiety, diarrhea, fatigue, gait instability, headache, insomnia, irritability, nausea and vomiting, tremor, visual disturbances and flu-like symptoms
    • Serotonin syndrome: MAOI, tramadol, dextromethorphan, meperidine, sympathomimetics, triptans, lithium, TCAs and SNRIs.  Symptoms include myoclonus, rigidity, tremors, incoordination, altered mental status, hypothermia, diaphoresis.  Use benzos and pressors for symptoms, cyproheptadine can be used to block serotonin
    • Patients may respond to a different SSRI or a SNRI if they don’t respond to one or they may want to change to another class.
    • May use a second agent to offset actions of another (using trazodone to treat SSRI induced insomnia)
    • Can add bupropion to SSRI if patient not responding
  • Tricyclic Antidepressants (TCAs): Limited use because of side effects.  Amitriptyline, imipramine, clomipramine, desipramine, nortriptyline.  They can cause orthostasis, conduction problems (increased QT), anticholinergic side effects, and withdrawn syndromes if abruptly discontinued.
  • Monoamine oxidase inhibitors (MAOIs): Non-selective – phenelzine and tranylcypromine.  Avoid tyramine-containing foods (aged cheese and meats) due to HTN crisis.
  • Mixed serotonergic meds: vilazodone, vortioxetine, trazodone, nefazodone, mirtazapine
  • Bupropion – decreases seizure threshold, may cause psychosis in susceptible individuals. May improve sexual dysfunction
  • Second generation anti-psychotics can be used to augment theraphy.  Most common: aripiprazole, brexipiprazole, quetipine.
  • Can try ketamine infusions, lithium, liothyronine, modanifil or scopolamine

Bipolar Disorder

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Manic Episode:

  • 1 week of abnormal and persistently elevated mood. inflated self-esteem, irritability, decreased need for sleep, flights of ideas, poor attention span, high-risk behaviors.
  • Bipolar 1: one or more manic or mixed episodes and major depressive episodes
  • Bipolar 2: one or more major depressive episodes accompanied by at least one hypomanic episode
  • Cyclothymic disorder: Periods of hypomania and depression that don’t meet criteria
  • Rapid cycling: Four episodes of mania or depression in one year.

Lithium:

  • Lithium is the gold standard for bipolar 1. Not good for unipolar depression, but has anti-suicidal effects in bipolar.  Effects take 1-2 weeks.  Most use antipsychotics or benzos during this period.
  • Initial lithium dose is 600-900mg/day in divided doses and then titrate.
    • Lithium has a narrow therapeutic index: 0.8-1.2 mEq/L.  A 300 mg increase can increase by 0.3 mEq/L.
    • >1.5 is toxic (GI complaints, tremor, altered mental status)
    • >2 can be lethal
    • Get trough 12 hours after last dose and every 1-2 weeks for 2 months and then every 3-6 months.
  • Get CBC, eletrolytes, renal function, thyroid function, urinalysis, ECG, and pregnancy test before starting.  Renal function test, thyroid test and urinalysis every 6-12 months
  • Lithium toxicity: lethargy, coarse tremor, confusion, seizures, coma and death
  • Renal impairment can increase dose
  • Avoid in pregnancy
  • Drug/Drug Drug/Food Interactions
    • Increase Lithium Concentrations: SSRIs, NSAIDs, ACE inhibitors/ARBs, Diuretics: thiazides, spironolactone, furosemide, metronidazole, tetracyclines, topiramate, medicines that affect electrolyte balance
    • Decrease Lithium Concentrations: theophylline, caffeine, Sodium bicarbonate and sodium chloride containing products, psyllium or ispaghula husk, urea, mannitol, acetazolamide, salt in food
    • Aggravate neurotoxicity:  haloperidol, risperidone, clozapine, phenothiazines, SSRIs, sumatriptan, tricyclic antidepressants, Calcium channel blockers, Carbamazepine, phenytoin, Methyldopa
    • Lithium can prolong the effects of Neuromuscular blocking agents
    • Anything that affects sodium or the kidneys affects lithium
  • Adverse effects: weakness, tremor, nausea, acne, hypothyroid, renal issues, polydipsia, hypercalcemia, parathyroid issues, calcium imbalance, confusion, leukocytosis, alopecia, weight gain, slurred speech, seizures
  • Lithium alternatives: carbamazepine (rapid cycling), oxcarbazepine (avoids some carbamazepine side effects), valproate without lamotrigine or lamotrigine with divalproex.