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The Medications of Addiction and Psychiatric Medicine- 2012

Merrill Norton Pharm.D.,D.Ph.,ICCDP-D Clinical Associate Professor University of Georgia College of Pharmacy Athens, Georgia mnorton@rx.uga.edu

Merrill Norton Pharm.D.,D.Ph.,ICCDP-D

Epocrates Monthly Prescribing Reference Facts and Comparisons Stahls Essential Psychopharmacology 3rd Edition Stahls The Prescribers Guide 4th Edition(2011) T-MAY Treatment of Maladaptive Aggression in Youth* (Just Released)

Clinical Handbook of Psychotropic Drugs Adults Children and Adolescents 19th Edition (Adult) 2nd Edition (Children) Updated Yearly www.scribd.com/doc/ 33609797/PrescribingGuidelines (Need Facebook account)
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FDA's Drug Safety Initiative Communication with the Public Index to Drug-Specific Information For patients, consumers, and healthcare professionals. Provides links to safety sheets with the latest risk information about the drug, related press announcements, and other fact sheets. Consumer Education: What You Need to Know to Use Medicine Safely Information to help patients and consumers work with health professionals to make the best medicine choices, buy safely, and use medicine so it's as safe and effective as possible. www.fda.gov/cder/drugSafety.htm

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Addiction ADHD Major

Depression Bipolar Disorder Psychotic disorders Anxiety Disorders/OCD

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Why Do People Abuse Prescription Drugs?

% of Basal Release

These prescription drugs, like other drugs of abuse (cocaine, heroin, marijuana) raise brain dopamine levels
frontal cortex

Dopamine
Neurotransmission

1100 1000 900 800 700 600 500 400 300 200 100 0

AMPHETAMINE

1 2 3 4 5 hr Time After Amphetamine

% of Basal Release

200 150 100 50 Empty Box Feeding 0 0 60

FOOD

nucleus accumbens

VTA/SN

Time (min)

120

180

Di Chiara et al.

BUT dopamine is also elevated by natural re-enforcers

CNS Actions of Corticotropin Releasing Factor (CRF)

Merrill Norton D.Ph.,NCAC II,CCS

Merrill Norton D.Ph.,NCAC II,CCS

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Allostasis - Definition
The ability to achieve stability through change To obtain stability, an organism must vary all of the parameters of its internal milieu and match them appropriately to environmental demands.

From: Sterling P and Eyer J, Allostasis: a new paradigm to explain arousal pathology. In Fisher S and Reason J (eds), Merrill Norton D.Ph.,NCAC II,CCS Handbook of Life Stress, Cognition and Health, John Wiley, New York, 1988, pp. 629-647.

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Allostatic Change in Mood State associated with Transition to Drug Dependence

Adapted from: Koob GF and Le Moal M, Neuropsychopharmacology, 2001, 24:97-129.

Merrill Norton D.Ph.,NCAC II,CCS

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Stimulants (Ritalin, Adderall) Act like Cocaine Directly in the Dopamine Cells
Distribution in the Human Brain of Cocaine and Ritalin

Cocaine

Ritalin

Cocaine and Ritalin Act on the Same Sites in Brain

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Pharmacokinetics in Human Brain

[11C]Cocaine
[11C]Methylphenidate

Relationship Between Drug Pharmacokinetics and the High

[11C]Cocaine
100

[11C]Methylphenidate
100 80 60 40 20

% Peak

80 60 40 20 0 0 10 20 30 40 50 60 70 80

"High"

"High"

0 10 20 30 40 50 60 70 80

Time (min)

Rate of Drug Uptake Into the Brain

Uptake in Striatum (%/cc)

Uptake in Striatum (nCi/cc)

0.06 0.05 0.04 0.03 0.02 0.01 0 0

iv cocaine

0.06
Uptake in Striatum (%/cc)

iv Ritalin

0.0035 0.003

oral Ritalin

0.05 0.04 0.03 0.02 0.01 0 0 20 40 60 80 100 120 Time (minutes)

0.0025 0.002

Fast!!!
20

Fast!!!

0.0015 0.001

Slow!!!
20 40 60 80 100 120 Time (minutes)

0.0005 00

40 60 80 100 120 Time (minutes)

Cocaine (iv) and Ritalin (iv) produce a high but Ritalin (oral) does not. The slow brain uptake of oral Ritalin permits effective treatment without a high.

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Development of Alternative Medications with no Drug Abuse Potential

Activation of CB2 Cannabinoid Receptors by AM1241Inhibits Experimental Neuropathic Pain

Suboxone Buprenorphine monotherapy product

Subutex Buprenorphine + naloxone combination product

Source: Ibrahim et al., PNAS, September 2, 2003.

(addition of opioid antagonist)

Medications to Treat Those Addicted

Effects of Buprenorphine Maintenance Dose on
-Opioid Receptor Availability


% Receptor Occupancy

94 to 98%
85 to 92%

100 90

80
70
60
50
40
30
20
10
0

27 to 47%

2 mg

16 mg

32 mg

Dose

Source: Greenwald, MK et al, Neuropsychopharmacology 28, 2000-2009, 2003.

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Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Brain Scan of ADHD- 1990

Dopamine in the Brain

Scientific American Http//www.sciam.com/1998/0998issue/0998barkely.html#link1

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The Neurobiology of ADHD Prefrontal Cortex LEFT BRAIN Locus Coeruleus Norepinephrine Dopamine Substantia Nigra RIGHT BRAIN

Corpus Callosum

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Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Stimulants Others-

Atomoxetine

remain the mainstay (SSRI) second line

Clonidine Guanfacine Bupropion

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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ADHD Diagnosis

Methylphenidate or Dexmethylphenidate

Dextroamphetamine or Mixed amphetamine salts

Dextroamphetamine or Mixed amphetamine salts

Methylphenidate or Dexmethylphenidate

Atomoxetine Or Bupropion

Tricyclic Antidepressants

2 agonist

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Atomoxetine

(Strattera)- SNRI- second line- 2 cases of hepatic damage Clonidine- less robust, concern for rebound HTN Bupropion (Wellbutrin)- Possible Utility in adults, substance abuse, etc.

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Amphetamines Clonidine Impriamine Methylphenidate Atomoxetine Guanfacine

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Dexmethylphenidate (Focalin XR) 5, 10, 15, 20mgs, isomer so theoretically half the methylphenidate dose Daytrana Patch (Daytrana), 14 hr duration, 10, 15, 20, 30mgs Lisdexamfetamine Dimesylate (Vyvanse) lasts 12 hours, prodrug need stomach to activate, 20, 30, 40, 50, 60, 70mgs
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Reduction Insomnia Anxiety Irritability

of appetite

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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HTN Stroke Sudden

death Heart attack Palpitations Arrhythmia

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Presynaptic Neuron Dopamine Norepinephrine (NE)

1. Selectively blocks the NE reuptake transporter located on the presynaptic neuron 2. Increases the concentration of NE in the synaptic cleft 3. Enhances the forward transmission of NE NE Receptor NE Transporter

Presynaptic Neuron Dopamine Norepinephrine (NE) NE Receptor

NE Transporter

Synaptic Cleft

Synaptic Cleft

Postsynaptic Neuron

Postsynaptic Neuron

The precise mechanism by which atomoxetine produces its therapeutic effects in ADHD is unknown
*Based on preclinical data; Bymaster F, et al. Neuropsychopharmacology. 2002;27:699-711. See Important Safety Information on slides 2531, including Boxed Warning, and full Prescribing Information for atomoxetine available during this presentation.

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Modafinil

(Sparlon, Provigil) (Nuvigil) Guanfacine( Intuniv)

Armodafinil

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Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level metaanalysis. JAMA. 2010;303:47-53.
Merrill Norton Pharm.D., D.Ph.,ICCDP-D 40

Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008;5:e45.
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Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905-1917. National Institute of Mental Health. Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. www.nimh.nih.gov/trials/practical/stard/index.shtml. Accessed Merrill Norton Pharm.D., D.Ph.,ICCDP-D December 28, 2010.

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Limbic System Prefrontal Cortex

Raphe Nuclei (5-HT source)

Locus Ceruleus (NE Source)

Cooper JR, Bloom FE. The Biochemical Basis of Neuropharmacology. 1996.

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Functional domains of Serotonin and Norepinephrine1-4

Serotonin (5-HT)
Sex Appetite Aggression

Depressed Mood Anxiety Vague Aches and pain Irritability Thought process

Norepinephrine (NE)
Concentration Interest Motivation

References:

Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms

2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43. 3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35. 4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.

1. Adapted from: Stahl SM. In: Essential Psychopharmacology: Neuroscientific Basis and Practical Applications: 2nd ed. Cambridge University Press 2000.

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Its not all in your head

Dysregulation of Serotonin (5HT) and Norepinephrine (NE) in the brain are strongly associated with depression Dysregulation of 5HT and NE in the spinal cord may explain an increased pain perception among depressed patients1-3 Imbalances of 5HT and NE may explain the presence of both emotional and physical symptoms of depression.
Adapted from References: 1. Stahl SM. J. Clin Psych. 2002;63:203-220. 2. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114. 3. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.

Descending Pathway Descending Pathway

Ascending Pathway

Ascending Pathway

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When to begin medications Psychotherapy Selection of meds

Length of treatment

Management of Depression

Dose titration

D/C of medications Non-response

Side Effects

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First

line therapy
Trade Celexa Lexapro Prozac Luvox Paxil Zoloft Initial Dose (mg/ day) 20 10 20 50 20 50 Dosage Range (mg/day) 20-60 10-20 20-60 50-300 20-60 50-200

Generic Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline

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Newer Agents Less sexual dysfunctions in some cases No more affective than TCAs or SSRIs Alternative option for resistant depression Indicated for major depression and generalized anxiety disorder
Generic Venlafaxine Duloxetine Desvenlafaxine Trade Effexor Cymbalta Pristiq 50 Initial Dose (mg/ day) 37.5-75 30 Dosage Range (mg/day) 75-225 30-90 50
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Merrill Norton Pharm.D., D.Ph., ICCDP-D Clinical Associate Professor University of Georgia College of Pharmacy Athens, Georgia mnorton@rx.uga.edu
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Cymbalta (duloxetine) Pristiq (desvenlafaxine) Viibryd (vilazodone)

Abilify (aripiprazole)

Symbyax (olanzapine/fluoxetine)
50

Manufactured by Lilly Comes as a delayed-release capsule 20mg, 30mg & 60mg strengths Approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, & chronic musculoskeletal pain Used off-label for urinary incontinence *Generic Time Released Formulation approved December 2011
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Manufactured by Wyeth Comes as an extended-release tablet 50mg & 100mg strengths Approved for major depressive disorder Used off-label for menopausal flushing
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Manufactured by Forest Labs Comes as an oral tablet 10mg, 20mg & 40mg strengths Approved for major depressive disorder

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Viibryd/ vilazodone hydrochloride

Pharmacology

Vilazodone is a novel agent that combines the anHdepressant acHvity of serotonin reuptake receptor inhibiHon with parHal agonist acHvity for 5HT1A, a common iniHal treatment for anxiety. However, the net eect of vilazodone on 5HT1A receptors is unknown.
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Viibryd package insert

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Dosing
Major depressive disorder: 10mg PO daily x 7d, then 20mg daily x 7d, then 40mg daily

55

Drug interactions Contraindicated for risk of serotonin syndrome: linezolid, methylene blue, tranylcypromine, isocarboxazid, selegiline, procarbazine, rasagaline Potential major interaction with warfarin, NSAIDs, and aspirin Potential major interaction with other SSRIs Other major interactions exist
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Generic Amitriptyline Clomipramine Doxepine Imipramine Desipramine Nortriptyline

Trade Elavil Anafranil Sinequan Tofranil Norpramin Pamelor

Initial Dose (mg/ day) 25 25 25 25 25 25

Dosage Range (mg/day) 100-300 100-250 100-300 100-300 100-300 50-200

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MOA: inhibition of MAO, the enzyme responsible for metabolizing norepinephrine, serotonin, dopamine Used in patients who do not respond to other antidepressants and/or to treat atypical depression Rarely used
Dietary restrictions Side effect profile Dangerous drug interactions Phenelzine (Nardil) Tranylcypromine (Parnate) Selegiline (Emsam)

Commonly used agents:

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High amounts of Tyramine

Smoked, aged, or pickled meat or fish Sauerkraut Aged chesses such as swiss and cheddar Fava beans

Moderate amounts of Tyramine

Beer, avocados, meat extracts, red wines

Low amounts of Tyramine

Caffeine-containing beverages, distilled spirits, chocolate, soy sauce, cottage & cream cheese, yogurt & sour cream
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1-2 weeks
Sleep Appetite Energy

2-4 weeks
Sadness Anhedonia

6-8 weeks
Full effects

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Depression Guideline Panel. Depression in Primary Care, Vol. 2: Treatment of Major Depression. Rockville, Md: US Dept of Health and Human Services, Public Health Service, and Agency for Health Care Policy and Research; 1993. Clinical PracHce Guideline No. 5.

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62

Uses: depression, extreme treatment resistant mania, psychosis, & seizures Electrode Placement: Bilateral: increases confusion/memory loss. Unilateral: decrease confusion/memory loss Treatment: 25 seconds in length minimum required for effect Number of treatments: 6-8 (12) in depression, more for mania (12-20) and psychosis (20-40) Side Effects: post-ictal confusion/ memory loss, headache, slight muscle soreness, nausea Medications
Anticholinergic: atropine or glycopyrrolate MI/IV before tx prevents aspiration and tachycardia Anesthesia: Methohexital IV. Pt is asleep when paralyzed Muscle relaxant: succinylcholine IV once anesthesia is complete prevents major muscle contractions and resultant bone fractures Oxygen: prevents hypoxia

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Uses: mild

anxiety, the blues, mild to moderate depression ONLY MOA: Serotonin reuptake inhibition, very minor MAOI occurs Side Effects: Mild and dose related: sedation, GI distress, photosensitivity, HA, and fatigue Dosing
Depression: bottle says 900mg/day (300mg TID) Drug Interactions: CYP450-3A4
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Data

from initial clinical trialsas likely as placebo to have suicidal thoughts or behaviors Possible explanationsImprovement Misdiagnosed? Irritability Withdrawal syndrome
Twice
Merrill Norton Pharm.D., D.Ph.,ICCDP-D 65

A US Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee (PDAC) has recommended approval of inhaled loxapine (Adasuve, Alexza Pharmaceuticals), as the first inhaled antipsychotic for agitation associated with schizophrenia and bipolar disorder (BD). FDA Psychopharmacological Drugs Advisory Committee Dec. 12, 2011 Women who experience a psychiatric episode in the immediate postpartum period appear to have an increased risk of developing bipolar affective disorder, according to the results of a new study. Trine Munk-Olsen, PhD; Thomas Munk Laursen, PhD; Samantha Meltzer-Brody, MD, MPH; Preben Bo Mortensen, DrMedSc; Ian Jones, PhD Arch Gen Psychiatry.Published online December 5, 2011. doi:10.1001/archgenpsychiatry.2011.157 Individuals with serious mental illness have a lifespan that is 15 to 20 years shorter than that of the general population in 3 countries with high-quality healthcare, new research shows. Br J Psychiatry. 2011;199:453-458, 441-442. Methodological issues like the inclusion of differing patient populations, differences in who (patients, family members, caregivers) received psychotherapy, and varying follow-up periods make it difficult to compare RCTs. Despite heterogeneous results, the majority of the studies showed relevant positive results in terms of reduced relapse rates, increased quality of life, better functioning or more favorable symptomatic outcome. Curr Opin Psychiatry.2011;24(6):549-555. HHS Guidance Could Help States Improve Oversight of Psychotropic Prescriptions in Foster Children GAO-12-270T, Dec 1, 2011
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Virani, A. S., Bezchlibnyk-Butler, K. Z., & Jeffries, J. J. (Eds.) (2011). Clinical Handbook of Psychotropic Drugs (19th ed.). Seattle: Hogrefe & Huber. ISBN: 978-0889373952. Bezchlibnyk-Butler, K. Z., & Virani, A. S. (Eds.) (2007). Clinical Handbook of Psychotropic Drugs for Children and Adolescents (2nd rev. ed.). Seattle: Hogrefe and Huber. ISBN: 978-0-88937-309-9. Schatzberg, A. F., & Nemeroff, C. B. (Eds.). (2009). The American Psychiatric Publishing Textbook of Psychopharmacology (4th ed.). Washington DC: American Psychiatric. ISBN: 978-1585623099. Hales, R. E., Shahrokh, N. C., Schatzberg, A. F., & Nemeroff, C. B. (2009). Study Guide to Clinical Psychopharmacology: A Companion to The American Psychiatric Textbook of Psychopharmacology, 4th Edition. Washington DC: American Psychiatric. ISBN: 978-1585623549 Stahl, S. M. (2008). Stahls Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (3rd ed). New York: Cambridge University Press. ISBN: 978-0521673761. Stahl, S.M.(2011) The Prescribers Guide (4th ed). New York : Cambridge University Press. ISBN: 978-0521173643. (Optional Text)
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Bipolar Disorder

Bipolar I

Bipolar II

Characterized by the occurrence of manic episodes with or without major depression episode

Characterized by at least one depressive episode with or without a hypomanic episode

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Affects 1% of the population First degree relative have increased rates of BPD-I, BPD-II, and MDD (4-24%)
Peak age of onset: adolescence through early 20s
Onset of first manic episode after age of 60 years is red flag to consider substance use or general medical condition

Season Variation
Depression more common in spring and autumn Mania more common in summer

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Bipolar I
Lifetime prevalence : 1% Women and men are equally affected Onset usually before age 30 No ethnic differences seen

Bipolar II
Lifetime prevalence: 0.5% Slightly more common in women Onset usually before age of 30 No ethnic differences seen

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Genetic
1st

Degree Relative with Bipolar Disorder: 8 to 18 times more likely to develop the illness Monozygotic twins: 75% Dizygotic twins: 5-25%

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Undiagnosed Bipolar Disorder -- Common and Concerning

Angst J, Azorin JM, Bowden CL, et al Arch Gen Psychiatry. 2011;68:791-798

Effects of Asenapine on Depressive Symptoms in Patients With Bipolar I Disorder Experiencing Acute Manic or Mixed Episodes
Armin Szegedi; Jun Zhao; Arjen van Willigenburg; Kari R Nations; Mary Mackle; John PanagidesEffects of Asenapine on Depressive Symptoms in Patients With Bipolar I Disorder Experiencing Acute Manic or Mixed Episodes

Antipsychotic Polytherapy in Bipolar Disorder- Is it more or less effective? BrooksJO; GoldbergJF; KetterTA; MiklowitzDJ; CalabreseJR; BowdenCL;
ThaseME Safety and tolerability associated with second-generation antipsychotic polytherapy in bipolar disorder: findings from the Systematic Treatment Enhancement Program for Bipolar Disorder.J Clin Psychiatry. 2011; 72(2):240-7

Are Cholesterol Levels Linked to Bipolar Disorder? One-year Risk of Psychiatric Hospitalization and Associated Treatment Costs in Bipolar Disorder Treated with Atypical Antipsychotics How Often Is Bipolar Disorder Disguised as Depression?
Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68:241-251.

Update on Antimanic Treatments: An Efficacy ComparisonYildiz A,Vieta E, Leucht S, Baldessarini RJ. Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology. 2011;36:375-389.
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MANIA!

MIXED EPISODE! HYPOMANIA!

NORMAL MOOD!

DEPRESSION!

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

Stahl S M, Essential Psychopharmacology (2000)!73

Euthymic

Start Treatment

Natural Course
Depressed

Treated Course

Acute

Continuation

Maintenance/ Discontinuation

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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First-line treatment of bipolar disorder Lithium Anticonvulsants (carbamazepine, valproic acid, divalproex) Olanzapine and other atypical antipsychotics

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Mood

Stabilizers Antidepressants Antipsychotics Anxiolytics Polypharmacy is the rule rather than the exception!

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FDA

approved age 13 and up evidence of multiple neurotransmitter effects (dopamine, serotonin, acetylcholine, NE, and GABA) Common SEs- thirst, GI, taste More troubling- tremor, acne Significant- renal, thyroid, ? Teratogenic
Mechanism-

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Bcl-2

Gray Matter

GSK-3

Manji HK, Moore GJ, Chen G, Biological Psychiatry 740-755, 2000 Merrill Norton 48: Pharm.D., D.Ph.,ICCDP-D

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Valproate Off

label use- few rigorous studies likely involves GABA, Protein kinase C, possibly kindling Monitor levels Common SEs- sedation, wt gain, GI Rare/Serious SEs-Teratogenic (neural tube), ?PCO, Hepatic damage, pancreatitis
Mechanism

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Carbamezepine-

off label- literature limited Autoinduction, leukopenia, rash, aplastic anemia, thrombocytopenia- use more infrequent Third Generation- Lamotrigine, Topirimate- literature limited, some promising info. Significant SEs include rash with Lamotrigine, weight loss with Topirimate
Merrill Norton Pharm.D., D.Ph.,ICCDP-D 80

Typical APs

(haloperidol, fluphenazine) less used-Atypicals more common Includes risperidone, quetiapine, olanzapine, ziprasidone Mechanism- D2 blockade + 5HT2 effects

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Na+

channel blocker and reduces glutamate release May be useful for refractory bipolar disorders including rapid cycling Slow titration due to the possibility of rash, which can lead to the StevensJohnson syndrome, which can be fatal.
See page 415 in the Anticonvulsant Therapy lecture.
Merrill Norton Pharm.D., D.Ph.,ICCDP-D 82

Positives

Negatives:

No blood tests Theoretically should be efficacious weight friendly

Higher rates of SIADH reported Twice a day dosing Little data Negative study

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

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Positives:

Negatives:

Very weight friendly No blood tests

Decreased cognitive dysfunction Little data Negative study

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Merrill Norton Pharm.D., D.Ph., ICCDP-D Clinical Associate Professor University of Georgia College of Pharmacy Athens, Georgia mnorton@rx.uga.edu
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Asenapine

(Saphris) Approved 2009 (Fanapt) Approved 2009 Lurasidone (Latuda) Approved 2010
Iloperadine

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Invega (paliperidone) Invega

Sustenna (paliperidone palmitate)

Saphris (asenapine maleate) Fanapt (iloperidone) Latuda (lurasidone)

Symbyax (olanzapine/fluoxetine)
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Manufactured by Janssen Comes as extended-release tablet 1.5mg, 3mg, 6mg & 9mg strengths Approved for schizoaffective disorder and schizophrenia

89

Manufactured by Janssen Comes as extended-release intramuscular injection 39mg, 78mg, 117mg, 156mg & 234mg singlesyringe strengths Approved for schizophrenia
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Manufactured by Merck Comes as sublingual tablet 5mg & 10mg strengths Approved for acute mixed or manic episodes in bipolar I disorder & acute treatment of schizophrenia
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Manufactured by Novartis Comes as oral tablet 1mg, 2mg, 4mg, 6mg, 8mg, 10mg & 12mg strengths Approved for schizophrenia

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Target

Dose 12-24 mg per day in BID dosing (Tritrate slowly to avoid orthostatic hypotension) ADE: Dizziness, Fatigue, Nasal Congestion, Tachycardia Not First Line Agent Due to QTcProlongation

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Manufactured by Sunovion Comes as oral tablet 40mg & 80mg strengths Approved for schizophrenia

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Pregnancy

Category B via P450 3A4 to two active and two inactive metabolites Dosage: 40-80mg once daily with Food( at least 350 calories) Food increases absorption Dose should NOT exceed 40mg with severe hepatic/renal impairment
Metabolized
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Atypicals

are not necessarily interchangeable-each has a unique profile, and may differ considerably re side effects Research data exists for risperidone in preschoolers

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Generic Aripiprazole Olanzapine Quetiapine Risperidone Ziprasidone

Trade Abilify Zyprexa Seroquel Risperdal Geodon

Initial Dosage (mg/ day) 20-30mg 10-15mg 50mg BID 2-3mg 40mg BID

Max Dose (mg/ day) 30mg 20mg 800mg 6mg 80mgBID

Approved for treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood stabilizing drugs Useful in psychotic/aggressive pts Aripiprazole & Olanzepine approved for maintenance

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GABA

is synthesized from glutamate GABA neurons act to dampen neuronal activity GABA receptors:
GABAA: Ionotropic control of a Cl- channel (IPSPs) GABAB: Metabotropic control of a K+ channel (IPSPs) GABAC: Metabotropic control of a Cl- channel (IPSPs)

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GABAA binding sites

Benzodiazepine site (increases channel frequency): anxiolytic Barbiturate site (increases channel duration) Steroid site (increases channel frequency) Picrotoxin site (inactivates the GABAA receptor)

GABAA receptors are comprised of subunits

(6),(4),(2)
Anxiolytic action of BZs requires 2 subunit Subunit configuration may change during chronic treatment (tolerance)

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Short Acting-Midazolam(Versed),Triazolam(Halcion) Immediate Acting-Alprazolam(Xanax),Estazolam (Prosom),Halazepam(Paxipam),Lorazepam (Ativan),Oxazepam(Serax), Temazepam(Restoril) Long Acting-Chlordiazepoxide (Librium,Libritabs), Clonazepam (Klonopin), Clorazepate (Tranxene), Diazepam (Valium),Flurazepam (Dalmane), Quazepam (Doral)

Merrill Norton Pharm.D., D.Ph.,ICCDP-D

101

Earlier

Identification and Aggressive Txmnt focus on primary and especially secondary Prevention Neurotransmitter and enzyme specific treatment. More delineation of Normal behavior and its relationship to our genes. More Exploration of Combined Therapy Remission not just response
Increase
Merrill Norton Pharm.D., D.Ph.,ICCDP-D 102

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