Pharmacology of
Antidepressants and Anti-anxiety
Agents
Aneet Ahluwalia, MD
Assistant Professor of Psychiatry and
Internal Medicine
Case
• 47-year-old woman presents to PCP with CC: fatigue.
She indicates that she was promoted to senior
manager in her company approximately 11 months
earlier. Although her promotion was welcome and
came with a sizable raise in pay, it resulted in her
having to move away from an office and group of
colleagues she very much enjoyed. In addition, her
level of responsibility increased dramatically.
• The patient reports that for the last 7 weeks, she has been
waking up at 3 AM every night and been unable to go back to
sleep. She dreads the day and the stresses of the workplace.
As a consequence, she is not eating as well as she might and
has dropped 7% of her body weight in the last 3 months. She
also reports being so stressed that she breaks down crying in
the office occasionally and has been calling in sick frequently.
When she comes home, she finds she is less motivated to
attend to chores around the house and has no motivation,
interest, or energy to pursue recreational activities that she
once enjoyed such as hiking. She describes herself as
"chronically miserable and worried all the time."
• Her medical history is notable for chronic neck
pain from a motor vehicle accident for which
she is being treated with tramadol and
meperidine. In addition, she is on propranolol
for hypertension. The patient has a history of
one depressive episode after a divorce that
was treated successfully with fluoxetine
• CBC, TSH, CHEM 7 WNL.
Criteria for Major Depression
-SIGECAPS, anhedonia or depressed mood,
impairment in functioning
Major Depression Epidemiology
• Point Prevalence males 2-3 %, females 4-9%
• Lifetime Risk males 7-12 %, females 20-25%
• Major Depression is 4th leading cause of disability
worldwide (this is probably an underestimate)
Risk Factors for depression
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Family history of mood disorder
Previous Episode
Stress
Emotional trauma
Childhood abuse/neglect
Elderly (over 65)
Marital factors (single, separated, divorced, or
unhappily married)
Risk Factors for depression-Cont
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Substance abuse
Physical illness
Heart disease
Diabetes
Obesity
Cancer
Menopause
Rhematoid arthritis
Prevalence of Depression in Medical Illnesses
Setting / Disease
Outpatient
Inpatient
Diabetes
Stroke
Cancer
Myocardial infarction
Rheumatoid arthritis
Parkinson’s disease
Prevalence Rate (%)
2-15
12
9-27
22-50
18-39
15-19
13
10-37
Musselman et al., Arch Gen Psych 1998, Biol Psych 2003; Cohen-Cole & Kaufman, Depression 1993
Depression-consequences
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Suicide
Suffering
Impaired relationships
Impaired job/school performance
negatively influence other medical conditions
and is a risk factor for medical M&M
• Co-morbid anxiety is common, and can
increase suicide risk
Genetics or Environment?
• Genetics and Environment both contribute
• Commonly accepted theory is that multiple gene loci
are implicated, and these loci make people more
vulnerable to environmental stressors, leading to
increased risk for MDD
• Why not one gene? Because depression is a
heterogeneous disorder that is not just one entity
(different subtypes of depression), with different
biological, psychological, and social causes
Presentation
• Adults can present with various somatic
complaints (such as lower back pain, headache,
CV, GI, GU) or decreased energy rather then
complaints of depression
• Elderly can present with cognitive deficits
(pseudodementia-poor effort) as well as somatic
complaints
Treatment
• Depression can be treated with
psychotherapy, with medication, or with the
combination of therapy and medication
• For moderate to severe, medication plus
therapy is the best option
• Placebo response ~0.4 compared to
antidepressant response ~0.7
Possible Biological Markers
• Decreased BDNF in serum
• Low tryptophan, 5HT, and 5HIAA (metabolite of 5HT)
in postmortem suicide patients
• Polymorphisms of 5HT1a receptors with decreased
affinity for 5HT have been shown to increase risk for
depression when stressed
• We can induce depression by tryptophan restriction
(tryptophan is a precursor to 5HT)
• Norepinephrine and Dopamine are thought to be low
in depression
Symptoms clusters and
Neurotransmitters
General Anxiety, obsessional depressive thoughts
Serotonin dysfunction
Anhedonia, psychomotor retardation
Dopamine dysfunction
Panic
Gaba dysfunction
fatigue, poor concentration
Norepinephrine dysfunction
Antidepressants/Antianxiety
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SSRIs-prevent reuptake of serotonin (5HT)
SNRIs-prevent reuptake of serotonin and NE
DNRI-prevent reuptake of NE and D
MAOI-prevent breakdown of monoamines
5HT1A partial agonist
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BZD/anticonvulsant-increase action of Gaba
Antihistamine
Block alpha 1, alpha2 agonist
Beta blockers
Brain Imaging findings in depression
• Decreased frontal blood flow (~7 %)
• Lower hippocampal volume
HPA-hypothalamic pituitary adrenal
axis
Stress causes a release of CRH, ACTH, and ultimately
cortisol. This is beneficial, as we need the increased
glucose it causes and increased blood pressure to
deal with the stressor at hand.
HPA- stress
• When exposed to chronic or extreme stress,
cortisol, ACTH, and CRH levels are at higher
levels, and stay elevated for longer periods of
time
So what? We’re not endocrinologists
• Cortisol and CRH have been shown to cause
damage to hippocampal neurons by causing
decreased dendritic branching and decrease in
pyramidal neuron spines
What does BDNF do?
• Promotes synaptic plasticity, neuronal growth,
neuronal spine formation, especially in
hippocampus
• Also helps cell survival and resilience
• Reduces apoptosis
• Shown to be low in patient with depression
• Increased BDNF expression in hippocampus of
depressed patients treated with
antidepressants compared to untreated
How do stress and hormones cause
these neuronal changes
• Stress and glucocorticoids supress expression
of Brain derived Neurotropic growth factor.
• Decrease in volume of hippocampus is
proportional to length of depression
• Prozac has been shown to increase
hippocampus synaptogenesis in rats after 5
days treatment (?mechanism of action?)
Examination of Cues-evolution
• LOSSES that cause sadness are of reproductive
resources
• Money, a mate, reputation, health, relatives,
friends….
• These things, in theory, would have increased
reproductive success (evolutionarily speaking)
LOSS = Signal of Maladaptive
Functioning
• If Loss triggers sadness
• And
• If sadness changes our behavior to stop
current losses, and prevent future ones….
• Then
• That would be useful, indeed!
Medical causes of depresion
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Hypothryoidism
Stroke
Multiple sclerosis
hyper/hypo parathyroidism
Addisons disease
Cushings disease
Hypopituitarism
Anemia
Anxiety Response Cues
Panic = fear imminent death
Social = fear embarrassment
PTSD = emotional memory of trauma
OCD = intrusive obsessions
GAD = free-floating; no conditioned
specific triggers
Generalized Anxiety Disorder
• prevalence of GAD of 5.1 percent to 11.9
percent. More common in women than men
(2 to 1)
• One of the most common illnesses you will
encounter in primary care as it is common in
the medically ill.
• Associated with increased health care
utilization
Generalized Anxiety Disorder aka
GAD
• Excessive worrying that is difficult to control
occurring more days than not for 6 months
causing significant distress/impairment
"Do you worry excessively about minor
matters?“
GAD
3 of the following symptoms
Restlessness
easy fatigued or poor sleep
difficulty concentrating
Irritable
muscle tension
GAD
• Usually fairly chronic
• Hereditary component—shared
neuroticism, depression and GAD
• Learned behaviors
• Environmental triggers
• GAD in adult life is associated with a higherthan-average number of traumatic
experiences and other undesirable life
events in childhood
GAD -treatment
• Therapy and meds both effective as is the
combination
• SSRIS first line, other agents helpful as well
such as SNRIs and BZDs
• Adjunctive treatment –accupuncture, yoga
can be helpful
Panic disorder
--classic, discrete episodes of intense fear that begin abruptly
and last for several minutes to an hour.
--often have chest pain, feeling of rapid heartbeat, or
shortness of breath – frequently precipitating an emergency
room visit.
--recurrent, unexpected panic attacks, and one month or
more of either worry about future attacks or consequences,
or a significant maladaptive change in behavior related to the
attacks, such as avoidance of the precipitating circumstances,
agoraphobia can occur.
Treatment for Panic
• Meds and Therapy are both equally effective,
combo is slightly better
• SSRIS first line, BZDs as well and SNRIs
OCD
OCD
Obsessions
contamination
pathological doubt
aggressive impulses
somatic concerns
need for symmetry
sexual impulses
OCD
Compulsions
cleaning
washing
checking
excessive ordering/arranging
counting
repeating
collecting
OCD
2-3% Americans (or 1 in 50)
Men=women
Onset generally in adolescence or early adulthood
Chronic waxing and waning course
Fist line treatments are SSRIs and CBT
Selection of Medication
• Family History of response
• Past treatment response
• Specific symptoms (with anxiety SSRI, Low energy
SNRI or WB)
• Medication interactions
• Medical conditions
• Side effect profile
• *important to educate about SE, what to expect,
and length of time for response to increase
compliance (don’t sensitize them)
SSRIs
prevent reuptake of serotonin
Take 2-6 weeks for full effect, usual length of
treatment at least 3-6 months
5HT1 - fights depression
5HT2 - tremors, sweating, decreased libido,
activation
5HT3 – nausea, diarrhea (ondansetron blocks
this receptor)
SSRIS
• Some DDIs- tramadol, mepiridine,
dextromethorpan, linezolid, tamoxifen,
clopidogrel
Fluoxetine=Prozac
-10-80 mg titrate to effect
-Long half life
-activating and ass with weight loss
-start at 10 & increase to 20 after ~1 week
-Inhibits 2D6 raising levels of beta blockers,
also lowers level of active metabolite of
clopidigrel, avoid with tamofixen
Citalopram and Escitalopram
• Citalopram is a mixture of 2 enantiomers while
escitalopram is just the more active enantiomer
• 5 mg escitalopram=10 mg citalopram
• Maximum mean prolongations in the QTc intervals
were 8.5 and 18.5 ms for 20 and 60 mg citalopram,
respectively
Sertaline=zoloft
• Start 25 and increase to 50. 200 mg max
• Effective, generic
• Most studied SSRI in pregnancy and breast
feeding and 1st line
• Inhibits 2D6--Increased beta blocker,
decreased active metabolite of tamofixen,
decreased levels of active metabolite of
clopidogrel
• More nausea/diarrhea than other SSRIS?
Paroxetine=Paxil
• Most sedating, most weight gain, worst
discontinuation syndrome
• Start at 10 mg and titrate up
• Has anticholinergic and antihistaminergic
activity
• DDIs - can increase beta blockers and lower
levels of active metabolite of tamoxifen
Fluvoxamine-luvox
• Marketed for OCD
• Not used as often
• 50-300 mg
SSRI possible side effects
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Appetite loss or Increase
Weight gain, weight loss
Nausea, Diarrhea
Decreased libido, delayed ejaculation or anorgasmia (10-30 %)
Akasthisia –inner restlessness (rare, usually at start)
Fatigue, sleepiness or sleeplessness (can use Benzos or newer
sleep medications as needed short term)
Long term use can cause apathy at high doses
Can cause hypomania or mania in bipolar patients
Dry mouth
Hyponatremia/SIADH (rare)
Vivid dreams
Increase in suicidal ideation in adolescents
QT prolongation
Rare serious side effects
• Serotonin syndrome- rare, presents with high fevers,
sweating, diarrhea, myoclonus, hyperreflexia,
muscle rigidity, tachycardia, hypertension, elevated
CK, nausea.
• Risk factors: combining SSRI and MAOI, using higher
doses and multiple serotonergic medications
(meperidine, tramadol)—also can cause seizure
• Dextromethorphan not contraindicated, but does
increase serotonin levels
• Treatment involves IV fluids and Benzos, dantrolene
can also be used.
• Perfect patient for SSRI
• Depression and anxiety patient in initial casethough consider tramadol decrease or
cessation
SNRIs
• Work by blocking reuptake of 5HT and NE
• Can be more activating due to NE aspect
• Norepinephrine aspect may be helpful for chronic
pain
• Dose dependent increase in BP in ~10% can be 10
mm
• Similar side effects to SSRIs but can have more GI
upset
Venlafaxine
• Venlafaxine-effexor 37.5mg-300, at lower
doses more serotonergic, at higher doses
more noradrenergic
• Significant discontinuation syndrome
Duloxetine
• 20 - 60 mg
• Also approved for fibromyalgia and diabetic
neuropathy
• not as severe discontinuation as venlafaxine
• DDIs - can increase beta blockers and lower
levels of active metabolite of tamoxifen
SNRI Perfect patient
• Depressed patient with anxiety symptoms,
low energy level, and chronic pain—diabetic
neuropathy or FMG
Bupropion
• Bupropion (wellbutrin) NE and Dopamine reuptake
inhibitor, 50-300 mg
• Works well for low energy (can augment SSRI), avoid
in highly anxious patients
• Also used for smoking cessation
• Low incidence of sexual dysfunction
• Lowers seizure threshold (dose related), relative
contraindication with epilepsy and bullemia, anorexia
• DDIs - can increase beta blockers and lower levels of
active metabolite of tamoxifen
DNRI patient
• Low energy depression, wants to quit
smoking, limited physical symptoms of
anxiety, wants to avoid sexual side effects, pt.
overweight
DDIs
• Tamofixen is metabolized by 2D6 into active
metabolites
• Plavix is metabolized by 2C19 into active
metabolites
Psychiatry and Medicine
• paroxetine, bupropion, fluoxetine, sertraline, duloxetine
inhibit 2D6-- to be avoided with tamoxifen (2D6)
• These same medications increase levels of many other
medications including beta-blockers.
• fluoxetine, sertraline inhibit 2C19 --avoid with clopidogrel
mirtazapine
• Good for anxiety/depression
• Blocks PRE synaptic alpha 2-adrenoceptors =
increasing synaptic 5HT and NE
• Blocks POST synaptic 5-HT 2 (less sexual SE) and H1
histamine receptors (Sedating, increased appetite
and weight gain)
• 5HT3 antagonist like ondansetron
• 7.5-30 mg, dose inversely proportional to sedation
Ideal mirtazapine patient
• On Chemotherapy for colon cancer-depressed,
anxious, nauseus, decreased appetite, weight
loss, poor sleep
Trazadone
Trazadone- Very sedating, often used to treat
insomnia, works as antidepressant at higher
doses, low sexual side effects
Antihistaminergic effect helps sleep
• Priapism (1/1000-1/5000) due to alpha 1
blockade
• Used as an adjunct to SSRIs for sleep
Tricyclic Antidepressants
• Prevent reuptake of 5HT and NE, helpful in chronic
pain
• Very effective, but not as well tolerated as SSRIs
• Alpha 1 blockade cause orthostatic hypotension and
dizziness
• Anticholinergic (blocks muscarinic receptors causing
dry mouth, blurred vision, urinary retention,
constipation)
• Antihistaminergic (blocks H1 causing sedation and
increased appetite/weight gain)
Tricyclic Antidepressants
• Use blood levels to monitor response and
compliance
• Can be lethal in overdose (2-3 grams) due to
prolongation of QT interval (treated with
bicarbonate)
Tricyclic Antidepressants
Tertiary amines
• Imipramine
• Amitryptiline
• Clomipramine
• Doxepin
Secondary amines
Desipramine
Nortryptiline
Protryptiline
less sedating
less hypotension
less anticholinergic
Discontinuation syndrome
• TCA : cholinergic rebound (sweating, N/V/D)
• SSRI : agitation, nightmares, anxiety,
dizziness, parasthesias (paroxetine worse than
other SSRIs)
• SNRIS: venlafaxine and cymbalta can have
worse discontinuation than SSRIs
• Prevention-slow taper
MAOI
• Monoamine Oxidase Inhibitors (MAOIs)
• MAO-A
--- metabolizes 5HT and NE selectively
--- metabolizes certain amines, linked to blood pressure
• MAO-B
--- protects neurons by metabolizing certain amines
such as protoxins into toxins that may cause
neuronal damage
MAOIs
MAOIs inhibit MAO in CNS, gut (leads to
increased tyramine absorption which
acts as false neurotransmitter and
elevates BP) hypertensive crisis
Avoid aged cheese/wines/tyramine foods
2 weeks to replenish MAO supply
Interactions: =, serotonin syndrome w/
SSRI/TCA- DC SSRI 2-5 wks before starting
MAOI (DC MAOI 2 wks before starting
SSRI), opioids (autonomic instability,
delerium, death), sympathomimetics,
oral hypoglycemic potentiation
MAOIs
• Classic MAOIs--irreversible and nonselective
• (MAO-A and B enzyme activity can not be restored
unless new enzyme is synthesized)
• Phenelzine, Tanylcypromine, Isocarboxazid
• Reversible and selective inhibitors of MAO-A (RIMAs)
• Moclobemide (antidepressant action)
Selegiline (now has a transdermal patch which at the
low dose 6 mg, has no diet restrictions)
What not to do
You are starting a pt. being treated for
MRSA/gram positive drug resistant infection on
an SSRI—what medication should you make sure
they are not taking?
Linezolid is an MAOI
What can you do?
Pt. with depression on celexa has a cough and
asks what he can take for his cough. What
shouldn’t he take?
dextromethorphan
Be aware
55 year old with chronic back pain currently
taking gabapentin, and norco alternating with
tramadol PRN. What DDI should you be aware
of before starting SSRI/SNRI?
Tramadol has SNRI activity—higher risk for
serotonin syndrome and seizure
PTSD: medications
SSRIs: ameliorate re-experiencing, avoidance,
hyperarousal
Alpha-adrenergics: prazosin helps with
nightmares
Beta- blockers
Can use other medications as well such as mood
stablizers and antipsychotics, evidence not as
good, lamotrigine has been shown to be
beneficial
Alpha 1 blockade
• Prazosin has been helpful in nightmares in
PTSD, start at 1 mg and titrate up as tolerated
– SE: sedation, orthostasis
Sedative-Hypnotics
GABA-ergic
Effects on GABAA Cl- Ion Channel
• GABA: Opens Cl¯ channel
• Binding sites:
•BZD, only w/GABA
•Enhance GABA affinity
•Barbituate, +/- GABA
•Prolong channel open time
•EtOH binding, +/- GABA
• Enhance GABA affinity
• Other binding sites
•non-BZD zolpidem/zoleplon,
picrotoxin, anti-convulsants
Sedative-Hypnotics
Benzodiazepines
• TYPE I (BZ1/omega1)
– Primarily in cerebellum
– Anxiolytic properties
– Less sedative properties
• TYPE II (BZ2/omega2)
– Located in cortex,
hippocampus, spinal cord
– NO anxiolytic properties
– Sedative & muscle-relaxant
properties of BZD
• TYPE III (omega3)
– Located in peripheral tissue
(kidney)
– NO anxiolytic properties
– ? Other properties
BZD Receptor Activity
FULL AGONIST
ANXIOLYTIC
PARTIAL
AGONIST
ANXIOLYTIC
ANTAGONIST
NO
CLINICAL
EFFECT
SED-HYPNOTIC
MYORELAXANT
ANTICONVULSANT
AMNESTIC
DEPENDENCY
Can cause
convulsion
PARTIAL
INVERSE
AGONIST
FULL INVERSE
AGONIST
PROMNESTIC
PROMNESTIC
ANXIOGENIC
ANXIOGENIC
PROCONVULSANT
CONVULSANT
Sedative-Hypnotics
BZD differences
BENZODIAZEPINES
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triazolam/Halcion 0.125-0.25 mg/d (short)
alprazolam/Xanax 0.75-4 mg/d (short)
oxazepam/Serax 30-120 mg/d (short)
chlorazepate/Tranxene 15-60 mg/d (intermediate)
lorazepam/Ativan 1-10 mg/d (intermediate)
estazolam/Prosom 0.5-2 mg/d (intermediate)
temazepam/Restoril 15-45 mg/d (intermediate)
clonazepam/Klonopin 0.5-5 mg/d (intermediate)
chlordiazepoxide/Librium 10-100 mg/d (long)
diazepam/Valium 2-40 mg/d (long)
flurazepam/Dalmane 15-45 mg/d (long)
quazepam/Doral 7.5-15 mg/d (long)
prazepam/Centrax 20-60 mg/d
halazepam/Paxipam 60-160 mg/d
BZDs are Evil
• Abuse potential
Decreased when properly prescribed and supervised
• Dependence
May occur at usual doses taken beyond several weeks
• Withdrawal
May occur even when discontinuation is not abrupt (e.g. by
10% Q3D); more likely after long-term treatment
Symptoms: tachycardia, HTN, mm cramps, anxiety, insomnia,
panic attacks, memory/concentration impairment,
perceptual disturbances, derealization, hallucinations,
hyperpyrexia, SZ.
Most common in Panic DO
• Rebound anxiety
Return of target symptoms, with increased intensity
BZDs Are Not Evil
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Rapid anxiolytic effect (30 mins)
No worsening of anxiety at initiation (like SSRI’s can)
Improve sleep onset and subjective quality
Extensive evidence of efficacy in MOST anxiety disorders (less true for
OCD, and not so true for PTSD)
Relatively safe in OD (winning favor over barbituates in 60’s)
Can Use 2-4 weeks to cover anxiety exacerbation caused by antidepressant initiation
Use PRN before exposure to a feared situation
Long term augmentation or mono-therapy is usually reserved for
treatment-resistant (to other anxiolytics)
buspirone (5HT1A partial agonist)
Pharmacodynamics/Pharmacokinetics
Onset of action: weeks (vs. days)
BID or TID dosing
NO sedation
NO performance impairment
NO cross-tolerance with BZD’s (BUT
response less favorable if pt recently
taken BZD ie. WD sx)
• NO tolerance or withdrawal
(compare w/ BZD and AD’s)
• NO abuse potential; safe in OD
• Demonstrated efficacy in GAD (to
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BZD);
• also augments MDD, OCD; useful in
aggression/agitation
• Strong 3A4 inhibitor
buspirone
Adverse Effects
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Nausea
Headache
Insomnia, nervousness
Restlessness
Dizziness, lightheadedness
• All minimized by slow ascending
regime (by 10mg q week)
clonidine/Catapres
guanfacine/Tenex
Alpha 2 agonist
Useful in blocking NE aspects of anxiety:
tachycardia, dilated pupils, sweating,
tremor; same for detox from
ETOH/barbs/heroin/BZD
Less powerful in blocking emotional aspects of
anxiety
Beta blockers
• For performance anxiety, block post synatpic
noradrenergic receptors—helps physical
symptoms of anxiety (racing heart, trembling)
OFF Label
• Zolpidem (an imidazopyridine); zaleplon (a
pyrazolopyrimidine)
– Bind near GABA site
– Use: mostly insomnia
– Caution: tolerance to effect is common, sleep behaviors
Melatonin can help sleep, Ramelteon
• Trazadone (brand name Desyrel)
– Dosing 50-100mg tid, maximum 400mg/day
– Cautions: postural hypotension; priapism
Off Label
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Sedating Antihistamines
– Examples
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Diphenhydramine (Benadryl)
Hydroxyzine (Atarax, Vistaril), 25-100mg/dose, up to 400mg/day
– Benefits: less-addictive, virtually no side effects
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Quetiapine and other new generation anti-psychotics
25-100mg/dose, bid-tid
– Uses: use as a anti-anxiety or sedative is off-label
– Benefits: non-addictive(?); no affinity at BZD-sites; 5-HT activity, possible
anti-depressant qualities
– Cautions: metabolic syndrome; tolerance to sedation; black box in
elderly; orthostasis
Chlorpromazine (brands: Thorazine
– 25-50mg tid
– Benefits: non-addictive, no metabolic syndrome, PO and IM
– Cautions: Ach, EPS (low risk)
Off label
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TCA’s (e.g., amitriptyline, nortriptyline, imipramine, doxepin)
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Use low doses 10-25mg tid; or 25-100mg qhs
Uses: sleep
Benefits: non-addictive
Cautions: cannot use PRN, cardiac adverse effects, lethality
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Barbituates
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Wellbutrin-NE/DE RUI -- bupropion can be activating, not used often
for anxiety
– Phenobarbtial, butalpital
– Addictive, very long acting
– In some common meds, e.g., fioricet
A word on…
ANTICONVULSANTS
• Related to BZDs and GABA
– Most seem to potentiate GABA
– Some may act on intracellular calcium channels
– Some block NMDA/glutamate (block excitatory NT, enhance inhibitory
effect)
– Sedation, Withdrawal, dizziness– renally cleared
• Gabapentin (Neurontin): At least 1 RCT shows effectiveness in
panic disorder and Social anxiety
• Lamotrigine (Lamictal): At least 1 RCT shows effect in PTSD
• Pregabalin (Lyrica):
– Many controlled RCTs with effect in GAD
– At least one RCT for pregabalin in Social phobia
Anticonvulsants
• Gabapentin and pregabalin-renally excreted no
hepatic metabolism. Side effects include sedation
and dizziness and edema. Tolerance, withdrawal, and
dependence are possible but less common than BZD
• Topiramate and zonisamide- carbonic anhydrase
inhibitors associated with weight loss
• Divalproex—monitor hepatic function, increased
weight