bipolar disorder depressive disorders...(f32.2) severe depressive episode without psychotic symptoms...

Bipolar Disorder

(F30) Manic episode

(F30.0) Hypomania

(F30.1) Mania without psychotic symptoms

(F30.2) Mania with psychotic symptoms

(F30.8) Other manic episodes

(F30.9) Manic episode, unspecified

(F31) Bipolar affective disorder

(F31.0) Bipolar affective disorder, current

episode hypomanic


episode manic without psychotic symptoms


episode manic with psychotic symptoms


episode mild or moderate depression


episode severe depression without psychotic

symptoms


episode severe depression with psychotic

symptoms


episode mixed

(F31.7) Bipolar affective disorder, currently in

remission

(F31.8) Other bipolar affective disorders

• Bipolar II disorder

• Recurrent manic episodes NOS

(F31.9) Bipolar affective disorder, unspecified

Depressive Disorders

(F32) Depressive episode

(F32.0) Mild depressive episode

(F32.1) Moderate depressive episode

(F32.2) Severe depressive episode without

psychotic symptoms

(F32.3) Severe depressive episode with

psychotic symptoms

(F32.8) Other depressive episodes

• Atypical depression

• Single episodes of "masked"

depression NOS

(F32.9) Depressive episode, unspecified

(F33) Recurrent depressive disorder

(F33.0) Recurrent depressive disorder, current

episode mild


episode moderate


episode severe without psychotic symptoms


episode severe with psychotic symptoms

(F33.4) Recurrent depressive disorder, currently

in remission

(F33.8) Other recurrent depressive disorders

(F33.9) Recurrent depressive disorder,

unspecified

Other Mood Disorders

(F38) Other mood (affective) disorders

(F38.0) Other single mood (affective)

disorders

• Mixed affective episode

(F38.1) Other recurrent mood (affective)

disorders

• Recurrent brief depressive

episodes

(F38.8) Other specified mood (affective)

disorders

(F39) Unspecified mood (affective) disorder

Adjustment Disorders

(F43.20) Adjustment disorder, Unspecified

(F43.22) Adjustment disorder, With anxiety

(F43.21) Adjustment disorder, With depressed

mood

(F43.24) Adjustment disorder, With disturbance

of conduct

(F43.25) Adjustment disorder, With mixed

anxiety and depressed mood

(F43.25) Adjustment disorder, With mixed

disturbance of emotions and conduct

Antidepressants

Drug Dosage FDA

indication

Benefits Risk/side effects PEARLS Special Considerations

SSRIs

Fluoxetine

(Prozac)

10-80mg/day

(start 20mg)

Depression,

Bulimia,

OCD, Panic

disorder

Activating, non-

selective,

inexpensive, long ½

life, little to no

discontinuation

syndrome

Headache,

Nausea, Tremor,

Sweats, Sexual

Side Effects,

Dulling of affect;

long ½ life with

active

metabolite; most

likely to induce

mania

Great for those with

substance abuse disorder or

long term depression

and/or treatment resistance

depression.

Dose in the morning

Not very serotonin

selective, also works on

norepi. Get big “bang for

your buck”

Potent 2D6 inhibitor

Citalopram

(Celexa)

10-40mg/day

(over 40mg

black box

warning). Start

20mg

Depression Mildly sedating,

Well tolerated, does

not interact with

most meds, easy

dosing range,

intermediate ½ life

Headache,

Nausea, sexual

side effects,

sedating; may

not be as

effective since it

is very selective;

QT prolongation

Great for those with mild

depression, or first episode

depression. Extremely

serotonin selective, no

norepi effects.

Can dose morning or

bedtime

Impairs Platelet Aggregation;

Risk of SIADH

Escitalopram

(Lexapro)

10-20mg/day;

10mg Lexapro=

20mg celexa

Depression,

Generalized

Anxiety

Disorder

Mildly sedating,

Very selective,

minimal side effects,

well tolerated, least

sexual side effects of

SSRIs

Headache,

Nausea

Will use when need a very

selective serotonin agent

but moderate-severe

depression.

Sertraline

(Zoloft)

50-200mg Day

(usually start

100mg/day)

Depression,

Panic, OCD,

PMDD,

PTSD, Social

Anxiety

Activating, only

SSRI safe in

cardiac disease,

short ½ life

Most GI side

effects; Sexual

Side Effects,

Large dose

range, BID

dosing for

tolerance at

200mg/day; max

absorption

requires full

stomach

Caution: May cause

agitation in the first week-2

weeks of treatment

especially in SSRI naïve

patients. Start low, go slow,

warn patients. Only take in

the morning to start.

Antidepressants

Paroxetine

(Paxil)

10-60mg/day Depression,

GAD, OCD,

Panic,

PMDD,

PTSD, Social

Anxiety

Mildly sedating;

short ½ life; no

active metabolite

Headache,

Nausea, sexual

side effects,

anticholinergic

side effects;

weight gain;

discontinuation

syndrome

I usually do not use as a

first line agent because of

side effects and drug

interactions.

Potent 2D6 inhibitor

Can potentiate bradycardia with

metoprolol; can decrease

analgesic effects with tramadol

SNRIs

Venlafaxine

(Effexor)

XR: 37.5-

225mg Daily

(don’t

recommend IR)

Depression,

GAD, Social

Anxiety,

Panic

Works well with

anxiety, depression,

ADD; Best 5HT to

NE ratio; usually

will know quickly if

effective; weight

neutral; short ½ life;

renal clearance

Severe

discontinuation

syndrome; Can

raise BP; Risk

with seizures;

Many people

cannot tolerate;

some QT

prolongation

Start low, go slow. Warn

about first week side

effects: sweating, agitation,

jaw clenching, dizziness,

problems with sleep.

About 10% of my patients

can’t tolerate for various

reasons

Can take several weeks to wean

off;

Desvenlafaxine

(Pristiq)

50mg/day (can

increase to

100mg/day but

limited benefit)

Depression,

Generalized

Anxiety

Disorder

Better tolerated than

Effexor; easy

dosing; quick

efficacy; works well;

weight neutral

Same as Effexor Will use when Effexor is

clinically effective, but side

effects are unbearable

Same as effexor

Duloxetine

(Cymbalta)

30-120mg/day Depression,

Generalized

Anxiety

Disorder;

Fibromyalgia;

Chronic Pain

Calming; quick

efficacy

Can increase

blood pressure;

can be overly

sedating; poorly

tolerated in some

Great to use with chronic

pain, fibromyalgia. Usually

my first line for these

people.

Moderate 2D6 inhibitor

Avoid in Renal and Hepatic

Dysfunction

TCAs

Amitriptyline 25-300mg/day

(QD or BID)

Depression Sedating; very

effective; can use to

augment SSRI

Sedating; cardiac

effects;

anticholinergic

effects;

orthostatic

hypotension

Works very well for sleep

or pm anxiety. Can use in

junction with SSRI

(monitor for serotonin

syndrome). Has serotonin,

norepi and dopamine

effects. Good for problems

with concentration

Major substrate of 2D6; avoid

with Alpha-1 antagonists or

Alpha-2 agonists; C/I in h/o MI

Antidepressants

Nortriptyline 25-150mg/day Depression Sedating; very

effective in chronic

pain/migraines; can

use with SSRI

Same Great for chronic pain. Has

serotonin, norepi and

dopamine effects

same

Imipramine 25- 300mg Depressio Stimulant effects;

can work as well or

better than

amphetamines in

ADHD

Some may not

tolerate; cardiac

effects;

anticholinergic

effects;

orthostatic

hypotension

same

Clomipramine 25-250 Depresion,

OCD

Same as

amitriptyline

Same as

amitriptyline

same

Others

Mirtazapine 15-45mg/day Depression Sedating, stimulates

appetite, very

effective, well

tolerated, can use to

augment SSRI

+++Weight gain Great first line drug for

mod-severe

depression/anxiety. Great

for elderly when appetite

stimulation needed.

Rare Agranulocytosis

Buspirone 5mg-20mg TID Anxiety Well tolerated;

calming; serotonin

effects

Headache,

nausea

3A4 substrate

Vortioxetine

(Brintellix)

10mg x 4 days

then 20mg

MDD Easy dosing; well

tolerated; no sexual

side effects

Still very new;

unknown

mechanism of

action; SIADH

Have not used on anyone

yet.

Mood Stabilizers

Drug Dosage FDA

indication


Antiepileptics (AED)

Divalproex Valrpoic Acid (Depakote, Depakote ER, Depakene) (blocks voltage-gated Na channels; increases GABA concentrations)

Load: 20mg/kg/day IR 500mg ER Adjust to VPA level of 50-125

Bipolar Disorder (acute Manic/Mixed) Approved for bipolar mania in children/teens Off label: anger, aggression, bipolar depression

Works great in individuals with anger, aggression, mania. ER dosing is once daily. IR formulation is cheap. Can be combined with lithium or Seroquel.

Hard on the liver, must monitor LFTs (monitor monthly, then q 3-6 mths). Must monitor drug levels q 3-6 mths. Weight gain.

Nausea, vomiting, tremor (treat with propranolol)

My go to med for males with bipolar d/o. Great for criminal population (anger, aggression, impulsivity control). Works well for control of anxiety. Can help with PTSD. Need higher dosing for ER as only 80% bioavailable Helpful with migraine control

Pregnancy Category D Do not use in pancreatitis/liver failure Must Taper to wean off (risk of withdrawal seizures) May lead to PCOS in females

Carbamazepine (Tegretol, tegretol XR) (Voltage gated Na-channel blockade; inhibits glutamate release)

Load: 200mg BID to max of 1600mg/day Goal CBZ level of 6-12

Bipolar Disorder Off label: anger, aggression

Works great in individuals with anger, aggression, mania. Works with irritability and anger in PTSD/Dissociative ID disorder.

Titrate slowly. Monitor LFTs/BMP/CBC/ EKG. It induces its own metabolism at first so may take up to a month for steady state

Most often used 2nd line. Will use when failed other mood stabilizers or in conjunction with lithium or antipsychotic. Some help with control of anxiety and PTSD. Helpful with neuropathic pain

Pregnancy Category D Must Taper to wean off (risk of withdrawal seizures) Risk of hyponatremia Risk of aplastic anemia, agranulocytosis Risk of Stevens-Johnson Syndrome 3A4 inducer

Oxcarbazepine (Trileptal) (Voltage gated Na-channel blockade; inhibits glutamate release)

300mg BID up to 1200mg BID Do not have to monitor drug levels, but drug levels can be tested

Off label: Bipolar Disorder

No weight gain. No drug monitoring needed.

Same risks as CBZ, but to less extent.

Great when carbamazepine works, but pt will not comply with drug level testing. Some help with control of anxiety and PTSD.

Decreases effectivness of BCP *Use highest dose estrogen BCP Risk of Hyponatremia Must Taper to wean off (risk of withdrawal seizures)

Mood Stabilizers

Lamotrigine (Lamictal) (Voltage gated Na-channel blockade; inhibits glutamate release)

25mg / day x 2 weeks 50mg / day x 2 weeks 75mg/day x 2 weeks 100mg / day x 2 weeks Max: 200mg/day Decrease by ½ when using with valproic acid Double dose if used with carbamazepine

Bipolar disorder

Works very well in bipolar depression. Weight neutral. No drug monitoring. Useful in treating aggression/agitation in TBI or dementia

Few adverse effects (headaches, dizziness, somnolence, nausea).

Works well in women, especially women with borderline PD in addition to bipolar. More effective than lithium for preventing depressive episodes. Will use for treatment resistant major depression. Also effective in treating anxiety. Will use in PTSD.

Risk of Stevens-Johnsons (< 1%, highest risk is during initial loading) Must Taper to wean off (risk of withdrawal seizures) Oral BCP may increase clearance

Topiramate (Topamax)

25mg BID up to 200mg BID

Off label for bipolar d/o

Rarely use as monotherapy in bipolar disorder

Mood Stabilizers

Other

Lithium (carbonate and Eskalith) (unknown MOA)

300 mg bid or tid 900 – 1200 mg maintence 1800 mg day ~ acute episode Serum Drug Levels: > 0.5mEq/L therapeutic 0.8 – 1.2mEq/L for acute episode 0.6 – 1.2mEq/L for maintenance > 1.5mEq/L is toxic

Bipolar maintenance, mania and depression

Inexpensive and effective. Neuroprotective effects (activates trophic actions at the synapse) Antisuicide properties

Weight gain, tremor (treat with Vit E 400mg BID), hair loss, polyuria, nausea/diarrhea Caution in renal disease √ renal function tests / thyroid / CBC with diff / lytes/ sp. gravity if renal disease do 24 h Cr clearance √ lithium level biweekly to start √ every 3-6 months… Use ER formulation if side effects problematic

My go to drug in females especially those with borderline PD and/or self harm, suicidal ideation. Use to augment antidepressant when chronic suicidal ideation is present. Also good for anger and irritability

Pregnancy Cat D 3% of patients develop goiter 5% of patients develop hypothyroidism Lithium is sodium bound ~ high serum sodium lowers lithium level low serum sodium elevates lithium level AVOID DEHYDRATION ~ SWEATING Risk for Lithium Toxicity (as low as 1- 1.5 mEq/L) Symptoms: tremors, cognitive impairment, fatigue, N/V/D, thirst, indigestion, weight gain, rash, hair loss, edema of legs (may need to stop med) *diarrhea can be severe / Δ lytes! *risk of diabetes insipidus *NOT with thiazide diuretic or NSAIDS Spironolactone if diurectic is needed *NOT in patients with renal failure

Antipsychotics in mood disorders

Drug Dosage FDA

indication


Atypicals (2nd generation)

Blocks D2 hyperactivity; reduces glutamate activity by different mechanisms; Serotonin 2A antagonism which causes efficacy in bipolar mania and psychosis Multiple mechanisms cause increased availability of serotonin, dopamine and norepinephrine which cause efficacy in bipolar depression

*CAUTION in folks with DM, hyper and hypglycemia weight gain is problamatic , cardiac problems / stroke akathesia, EPS, tartive dyskansia Monitor weight, lipids and A1C

Risperidone (Risperdal)

0.5mg – 6mg Consta – 25mg-75mg IM q 2 wks

Bipolar mania/mixed /maintenance

few anticholinergics side effects. Mild sedation. Once a day or BID dosing time to peak: 1 hr

↑ risk for movement disorders ↑prolactin

Most “typical” of the atypicals as dose rises Cheap and very effective, usually well tolerated. One of my first lines as it has less sedation/weight gain of other inexpensive atypicals

2D6 substrate Primarily renal excretion (care in renal disease) Caution in hepatic impairment

Olanzapine (Zyprexa)

5mg – 20mg, but frequently used up to 30mg/day

Bipolar mania/ mixed depression/ maintenance

↓ EPS Mildly sedating Does not raise prolactin Time to peak: 6 hrs

↑ ↑ weight gain, greatest cardiometabolic effects

Improves mood in bipolar and depression especially when combined with fluoxetine. Available in ODT, but time to onset no quicker

2D6 substrate Rare DKA/HHNK Smoking will reduce levels Caution in hepatic impairment

Quetiapine (seroquel)

25mg-800mg/day

Bipolar mania/ depression/ maintenance XR formulation: depression augmentation

Virtually NO EPS / TD. No prolactin. helps with sleep onset

very sedating weight gain cardiometabolic effects (less than Zyprexa) QTC prolongation risk (ave 12ms): monitor EKG and care with other QTC prolonging agents

Lack of EPS makes it preferred in parkinsons and bipolar/schizophrenia. Good antidepressant action Start low and go slow in naïve patients.

3A4 substrate (fluoxetine will increase levels, CBZ will decrease levels) Primarily renal excretion (care in renal disease) Caution in hepatic impairment Caution in seizure disorder

Antipsychotics in mood disorders

Ziprasidone (Geodon)

20mg to 80mg BID

Bipolar mania/mixed/ maintenance

Low EPS Low prolactin effects no weight gain lowers lipid levels mild sedation

NOT with electrolyte problems QTC prolongation risk (ave 20ms): monitor EKG and care with other QTC prolonging agents

Works better at higher doses than lower, so quick uptitration increased uptake with food Antidepressant and anxiolytic effects Good less expensive alternative to abilify if metabolic effects are concerning

3A4 substrate(fluoxetine will increase levels, CBZ will decrease levels) Safer in renal disease (PO formulation) Caution in CHF

Aripriprazole (Abilify)

2.5mg – 5mg to 30mg / daily slowly

Bipolar mania/mixed/ maintenance Depression Augmentation

no weight gain little to no cardiometabolic effects

↑ risk for movement disorders/ akathisia Activating, very little sedation Now generic, but still VERY expensive ($20-$30 a PILL)

Works well in treating mania, aggression, agitation Slow time to steady state: ½ life is 75 hrs! Not effective as a single agent when speed is needed

2D6 substrate 3A4 substrate (fluoxetine will increase levels, CBZ will decrease levels)

Lurasidone (Latuda)

201-120mg/day Bipolar Depression

No weight gain little to no cardiometabolic effects little risk for EPS

Well tolerated Mild sedation Nausea Brand only so expensive

Must take with small meal (400cal) Minimal cognitive effects Anxiolytic effects For some reason I have had the best result in African American females.

Caution in renal and hepatic impairment

bipolar disorder depressive disorders...(f32.2) severe depressive episode without psychotic symptoms...

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