The Black Book of Psychotropic Dosing and Monitoring

Introduction

Psychopharmacology Bulletin is well into its sixth decade of publishing. During that time, psychopharmacology has advanced as a medical discipline by maximizing research into the biological causes of psychiatric disorders.

For many academics and clinicians, biological and psychopharmacological approaches have become the mainstay of psychiatry. The profound shift in the treatment of psychiatric disorders has been fueled by new developments that have come in several forms—from novel drugs to new indications for older agents. Advanced formulations of previously released drugs may now allow for more convenient dosing and administration.

Since the last update of The Black Book in 2007, new psychotropics have expanded existing classes of drugs, while others have challenged the well-worn nomenclature of psychiatric agents. For example, the first serotonin–norepinephrine reuptake inhibitor (SNRI), venlafaxine, was introduced in 1994. Since then, other SNRIs like atomoxetine (Strattera)—a norepinephrine-predominant SNRI used in the treatment of ADHD since 2002—and, two years later, Duloxetine (Cymbalta) were approved for the treatment of depression, neuropathic pain, major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic neuropathy, chronic musculoskeletal pain, including chronic osteoarthritis pain and chronic lower back pain. Four years later, the FDA approved desvenlafaxine (Pristiq)—the active metabolite of venlafaxine, followed by milnacipran (Savella, Toledomin, Ixel) for the treatment of depression and fibromyalgia. Levomilnacipran (Fetzima)—the levorotating isomer of milnacipran—was approved by the FDA for treatment of MDD in July 2013.

Two neuroscience-based nomenclature serotonin multimodal (S-MM) agents have been approved for MDD: vilazodone (Viibryd) and vortioxetine (Trintellix, formerly Brintellix). Vilazodone is a serotonin partial agonist reuptake inhibitor (SPARI) and a dual-acting 5HT1A partial agonist, used for MDD and off-label for anxiety and obsessive-compulsive disorder (OCD). Like vortioxetine, vilazodone has a beneficial profile as it applies to weight gain and sedation. Threatening side effects such as seizures, induction of mania, and activation of suicidal ideation, are rarely seen in either agent. Vortioxetine is used off-label for generalized anxiety disorder, cognitive symptoms associated with depression, and geriatric depression. Sexual dysfunction has been noted in some patients, but at significantly lower rates than for SSRI-class antidepressants. Vortioxetine’s pro-cognitive side effects and use in the elderly are especially notable. Equally worthy of mention is Flibanserin (Addyi), the first FDA-approved agent for generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.

Second-generation antipsychotics (SGAs/atypicals), which include clozapine (Clozaril), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodone), aripiprazole (Abilify)—and, more recently, paliperidone (Invega), iloperidone (Fanapt), lurasidone (Latuda), and asenapine (Saphris) have now largely supplanted first-generation “typical” antipsychotics such as perphenazine and haloperidol. The SGAs may be more helpful than typical agents in treating the negative symptoms of schizophrenia, but not all clinical trials bear that out. Perhaps of the most importance, it is clear that virtually all of the SGAs are effective antimanic drugs and probably work faster than mood-stabilizing agents such as lithium.

The anticonvulsant class of agents have been a source of great study in the treatment of bipolar disorder since the anticonvulsant, lamotrigine (Lamictal), became only the second drug approved for use in the maintenance and treatment in bipolar patients. Other anticonvulsant-class drugs are being studied. They include gabapentin (Neurontin), pregabalin (Lyrica), topiramate (Topamax), tiagabine (Gabitril), ethosuximide (Zarontin), zonisamide (Zonegran, Excegran), and levetiracetam (Keppra).

For the purposes of the 2018 Black Book, the advance toward effective and well-tolerated anxiolytics and hypnotics has been stymied for a variety of reasons. Although clinicians have a number of effective anti-anxiety agents to choose from, there are still significant limitations to the available agents. The benzodiazepines, while rapidly acting and effective, carry the risk of dependence and cognitive side effects. Antipsychotics have well-known limitations and are considered third-line agents. Many clinicians regard buspirone as a weak anxiolytic at best.

For the past 30 years, the efforts to develop better hypnotics have focused entirely on chemicals that bind to some form of benzodiazepine receptor. So far, this systematic approach has yielded a handful of agents—zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta), and zopiclone (Imovane)—that are active at benzo-receptors but are not chemically benzodiazepines. Though none of these agents is remarkably different from benzodiazepines, the non-benzo hypnotics have some advantages in that they are less likely to cause rebound insomnia or to exacerbate obstructive airway problems through muscle relaxation, and may show continued efficacy, when given nightly, for much longer.

Along with benzodiazepines, stimulants continue to pose unique problems for the clinician. The good news is that a number of new stimulant dosing options have become available over the last 10 years. Novartis, the manufacturer of Ritalin and Ritalin SR, has developed Ritalin LA (long acting), designed to release half of each dosage quickly and the other half slowly. Novartis has also obtained pure d-methylphenidate (Focalin), which is twice as potent as racemic Ritalin.

To add options (and perhaps confusion) to the field, Celltech pharmaceuticals introduced a long-acting methylphenidate (Metadate CD), which produces about eight hours of effect. A transdermal methylphenidate patch, Daytrana, has recently become available. Lisdexamfetamine (Vyvanse) represents another approach: once-a-day dosing. Lisdexamfetamine is essentially a pro-drug that is metabolized to dextroamphetamine. It has been studied in ADHD and shown to be effective at doses of 30–70 mg taken in the morning. (500) In 2009, guanfacine (Intuniv, Tenex), in its extended-release formulation, became the second non-stimulant to be approved for the treatment of ADHD. Guanfacine, used historically as an antihypertensive, may signal an area of future research.

New to this edition is the inclusion of drugs used for substance use disorders. These agents are new and frequent subjects in the popular press, but they remain a frustrating lesson in incremental progress for experts in the field. The most positive research into opiate addictions is the continuing results of buprenorphine (Suboxon, Probuphine implant) therapy as an alternative to methadone treatment. Buprenorphine, Butrans (transdermal patch), and Suboxone (buprenorphine and naloxonel, a mixed agonist-antagonist) have allowed for the possibility of an office-based treatment outside of highly regulated methadone clinics. Studies support that outpatient buprenorphine treatment is highly effective in reducing relapse and may be safer than methadone treatment (Bell et al. 2009; Parran et al. 2010). The drug given usually at dosages of 6–20 mg/day, with a target dosage of around 16 mg/day.

New medications for dementia and Alzheimer’s disease (AZ) continue to confound researchers, despite vigorous efforts. Since the mid-1990s, the FDA has approved a number of cholinesterase inhibitors (CIs) to treat mild to moderate AZ have been approved by the FDA. Currently, the most commonly prescribed CI is donepezil (Aricept), which has shown to have a modest effect in slowing the progression of AZ. Two other CIs, rivastigmine (Exelon), and galantamine (Reminyl), have been equally unsuccessful in slowing the progression of AZ, but they do show an improvement in the quality of life in some patients. In 2003, memantine (Namenda) became the first drug to be approved for moderate to severe AZ. Memantine is a moderate N-methyl-D-aspartate (NMDA) antagonist that is thought to mitigate the toxic effects of increased calcium flow into neurons by blocking NMDA receptors. Memantine appears to improve cognition significantly more than placebo in patients with moderate or more severe dementia.

Additionally, patients who are already taking a CI, appear to improve with the addition of memantine (Reisberg et al. 2003, Tariot et al. 2004).

Two high-profile clinical trials into new AZ drugs manufactured by major pharmaceutical companies were discontinued recently. The most promising new AZ drug on the horizon is Biogen’s aducanumab—an antiamyloid drug. Biogen’s data from early Alzheimer’s disease patients who have been taking the drug for two to three years is promising. Aducanumab is currently being evaluated in two global Phase III studies, ENGAGE and EMERGE, with the first data emerging sometime after 2020.

The jury is still out on anorexiants as effective weight management tools. New agents such as lorcaserin (Belviq, Belviq XR) join newly approved dual compounds such as naltrexone-bupropion (Contrave) and phentermine-topiramate (Qsymia) in the quest to ally one of the holy grails of medicine, obesity.

The 2018 Black Book provides practical information regarding many different psychotropic drugs. We have included information derived from our reading of the psychiatric literature as well as from our own clinical practice. As with previous editions, the 2018 edition of this monograph is aimed at providing the clinician with an up-to-date set of tables and the framework for applying an ever-expanding list of psychotropic agents in clinical practice.

This work is written as a practical, usable, clinical guide. We have provided at the end of The Black Book a list of selected, relevant articles and books for readers who want to go beyond the material presented here.

— Editorial Director, James M. La Rossa Jr., contributed to the 2018 update of The Black Book

Table 1. Psychotropic Drug Dosage Ranges.

GENERIC	BRAND NAME	DOSAGE RANGE* (MG/DAY)
Alprazolam	Xanax Xanax XR	1–4
Amantadine	Symmetrel	100–300
Amisulpride	Soilan	400–1200
Amitriptyline	Elavil	50–300
Amoxapine	Asendin	200–600
Amphetamine-D	Dexedrine	5–40
Amphetamine/dextroamphetamine	Adderall Adderall Xr	5–40
Aripiprazole	Abilify	2–30
Armodafinil	Nuvigil	150–250
Asenapine	Saphris	10–20
Atomexetine	Strattera	40–100b
Benztropin	Cogentin	0.5–6
Biperiden	Akineton	2–24
Blonanserin	Lonasen	8–16
Brexpiprazole	Rexulti	2–4
Buprenorphine	Suboxon (w/Naloxone) Probuphine Implant	8–32
Bupropion	Wellbutrin	200–450
	Wellbutrin SR
	Wellbutrin XL
Buspirone	BuSpar	20–60
Carbamazepine	Tegretol	400–1,600
	Tefgretol XR
	Carbatrol
Cariprazine	Vraylar	1.5–6
Chlordiazepoxide	Librium	15–40
	Limibitrol
	Librax
Chlorpromazine	Thorazine	200–800
Citalopram	Celexa	20–40
Clomipramine	Anafranil	100–250
Clonazepam	Klonopin	0.5–4
Clonidine	Catapres	0.1–0.4
	Kapvay
	Duraclon (Injectable)
Clorazepate	Azene	15–60
	Tranxene
Clozapine	Clozaril	25–700
	Leponex
	Versacloz (oral suspension)
	Fazaclo ODT (oral tablets)
Desipramine	Norpramin	100–300
Desvenlafaxine	Prestiq	50–100
Dextromethorphan	Nuedexta	10–20
Diazepam	Valium	4–40
Diphenhydramine	Benadryl	50
	Sominex injection:	10–50
D-methamphetamine	Desoxyn	20–25
Disulfiram	Antabuse	250–500
Donepezil	Aricept	5–10
Doxepin	Sinequan	75–150
	Silenor
Droperidol	Inapsine	2.5–15
Duloxetine	Cymbalta	60–120
Escitalopram	Lexapro	10–40
Estazolam	ProSom	1–4
Eszopiclone	Lunesta	1–3
Ethosuximide	Zarontin	15–40
Flibanserin	Addyi	100
Fluoxetine	Prozac	20–80
	Sarafem
Flupenthixol	Depixol	3–6
Fluphenazine	Prolixin	1–40
Fluphenazine decanoate	Prolixin Decanaote	1–20
Flurazepam	Dalmane	15–30
Fluvoxamine	Luvox	100–300
	Luvox CR
Gabapentin	Neurontin	900–3,600
	Gralise (XR)
	Horizant (XR)
Galantamine	Reminyl	16–24
	Razadyne
Guanfacine XR	Intuniv	1–4
	Tenex
Haloperidol	Haldol	1–40
Haloperidol decanoate	Haldol Decanaote	50–100 mg/mL
Hydroxyzine	Atarax	50–100
	Marax
	Vistaril
Iloperidone	Fanapt	12–32
Imipramine	Tofranil	150–300
Imipra mine Pamoate	Tofranil-PM	150–300
Isocarboxazid	Marplan	40–60
Lamotrigine	Lamictal	100–400
	Lamictal ODT
	Lamictal XR
Levetiracetam	Keppra	1000–3000
	Keppra XR
Levomilnacipran	Fetzima	40–120
Lisdexamfetamine	Vyvanse	30–70
Lithium carbonate	Eskalith	600–1,800
	Eskalith CR
	Lithobid (slow release)
Lofepramine	Deprimyl	140–210
	Gamanil
Lorazepam	Ativan	1–6
Loxapine	Loxitane, Adasuve	20–250
Lurasidone	Latuda	20–80
Maprotiline	Ludiomil	75–225
Memantine	Namenda	5–28
	Namenda XR
Mesoridazine	Serentil	100–400
	Lidanil
Methylphenidate (D, L)	Concerta	18–72
	Ritalin, Ritalin-SR	10–60
	Ritalin LA, Metadate ER
	Metadate CD	20–60
	Methylin (chewable)
	Methylin ER
	Daytrana (Trans. Patch)
	Focalin	5–30
	Focalin XR	10–40
Mianserin	Lerivon	30–90
Milnacipran	Savella	100–200
	Ixel
	Toledomin
Mirtazapine	Remeron	15–45
Moclobemide	Aurorix	300–600
	Arima
	Manerix
Modafinil	Provigil	50–800
	Alertec
	Modiodal
Molindone	Moban	40–225
Naltrexone	Revia	50–150
	Vivitrol (injection)	380 mg/4 wks
Naltrexone-Buproprion	Contrave	16/180 bid
Nefazodone	Dutonin	300–600
Nortriptyline	Pamelor	50–300
Olanzapine	Zyprexa	5–20
	Symbyax (olanzapine-fluoxetine)	6–12/25–50
Oxazepam	Serax	15–120
Oxcarbazepine	Trileptal	600–2400
	Oxtellar XR
Paliperidone	Invega	6–12
Paliperidone palmitate	Invega Sustenna
Paroxetine	Paxil	20–50
Paxil CR
Perphenazine	Trilafon	12–64
Phenelzine	Nardil	45–90
Pimavanserin	Nuplazid	34
Pimozide	Orap	1–10
Pregabalin	Lyrica	150–600
Procyclidine	Kemadrin	5–20
Propranolol	Inderal	40–400
	InnoPran XL
Protriptyline	Triptil	15–60
	Vivactil
Quazepam	Doral	7.5–30
Quetiapine	Seroquel	50–800
	Seroquel XR
Ramelteon	Rozerem	8
Reboxetine	Norebox	2–10
	Erdonax
Risperidone	Risperdal	2–16
	Risperdal M-Tab
	Risperdal Consta
Rivastigmine	Exelon	6–12
Selegiline	Eldepryl	20–60
	Emsam (patch)
Sertindole	Serdolect	12–24
Sertraline	Zoloft	50–200
Sodium Oxybate	Xyrem	6–9 g/night
Sulpiride	Dolmatil	150–2400
Suvorexant	Belsomra	10–20
Tasimelteon	Hetilioz	20
Temazepam	Restoril	15–30
Thioridazine	Mellaril	200–800
Thiothixene	Navane	5–60
Tiagabine	Gabitril	4–56
Tianeptine	Coaxil	37.5
	Stablon
	Tatinol
Topiramate	Topamax	200–400
	Qudexy XR
	Trokendi XR
Tranylcypromine	Parnate	30–60
Trazodone	Desyrel	150–600
Trazadone XR	Oleptro	150–375
Triazolam	Halcion	0.125–0.5
Trifluoperazine	Stelazine	2–6
Trihexyphenidyl	Artane	2–30
Trimipramine Maleate	Surmontil	50–300
Valproic Acid/750–4,200	Depakene	500–1500
Valproate sodium	Depacon
Divalproex sodium	Depakote
Venlafaxine	Effexor, Effexor XR	75–375
Varenicline	Chantix	0.5–4
Vilazodone	Viibryd	40
Vortioxetine	Trintellix	10–20
Zaleplon	Sonata	10–20
Ziprasidone	Geodon	40–200
Zolpidem	Ambien	5–10
	Ambien-CR
Zonisamide	Zonegran	100–600
	Excegran
Zopiclone	Imovane	7.5
Zotepine	Lodopin	75–300
	Zoleptil
Zuclopenthixol	Clopixol	20–60

Table 2. Mood Disorders—Antidepressants: Names, Formulations, Strengths, and Dosages.

GENERIC NAME	BRANDa NAME	FORMULATIONSb AND STRENGTHS	USUAL THERAPEUTIC DOSAGE (MG/DAY)c
A: SSRIS
citalopram	Celexa	Tablets: 10, 20, 40 mg	20–40
		Oral solution: 10 mg/5 mL (240-mL bottle)
escitalopram	Lexapro	Tablets: 5, 10, 20 mg
		Oral solution: 5 mg/5 mL (240-mL bottle)
fluoxetine	Prozac	Capsules: 10, 20, 40 mg	20–60
		Capsule (weekly): 90 mg
		Oral solution: 20 mg/5 mL (120-mL bottle)
		Tablets: 10, 20mg
fluvoxamine	Luvox	Tablets: 25, 50, 100 mg	100–200
	Luvox CR	Tablets: 100, 150 mg
paroxetine	Paxil	Tablets: 10, 20,30, 40 mg	20–50
		Oral suspension: 10 mg/5 mL (250-mL bottle)
		Tablets: 12.5, 25, 37.5 mg
	Paxil-CR (controlled-release)
sertraline	Zoloft	Tablets: 25, 50, 100 mg	50–200
		Oral concentrate: 20 mg/mL (60-mL bottle)
5-HT2 ANTAGONISTS
nefazodone	Generic only	Tablets: 50, 100, 150, 200, 250 mg	300–500
trazodone	Generic only	Tablets: 50, 100, 150,d 300d mg	150–300
	Oleptro (extended release)	Tablets (scored): 150, 300 mg	150–375
OTHER
bupropion	Wellbutrin and generic	Tablets; 75, 100 mg	200–450
	Wellbutrin SR (sustained-release)	Tablets: 100, 150, 200 mg
	Wellbutrin XL (extended-release)	Tablets: 150, 300 mg
mirtazapine	Remeron	Tablets: 7.5, 15, 30, 45 mg	15–45
		Soltabs: 15, 30, 45 mg
vortioxetine	Brintellix	Tablets: 5, 10, 20 mg	10–20
vilazodone	Viibryd	Tablets: 10, 20, 40 mg	40
B: SNRIS
venlafaxine	Effexor	Tablets: 25, 37.5, 50, 75, 100 mg	75–375
	Effexor-XR (sustained-release) and generic	Capsules: 37.5, 75, 150 mg
desvenlafaxine	Prestiq	Tablets (extended release): 50, 100 mg	50–100
duloxetine	Cymbalta	Capsules: 20, 30, 60 mg	60–120
levomilnacipran	Fetzima	Capsules: 20, 40, 80, 120 mg	40–120
milnaciprane	Savella	Tablets: 12.5,25, 50, 100 mg	100–200
C: TRICYCLICS
amitriptyline	Elavil	Tablets: 10, 25, 50, 75, 100, 150 mg	150–300
clomipramine	Anafranil	Capsules: 25, 50, 75 mg	100–250
desipramine	Norpramin	Tablets: 10, 25, 50, 75, 100, 150 mg	150–300
doxepin	Sinequan	Capsules: 10, 25, 50, 75, 100, 150 mg	150–300
		Oral solution: 10 mg/mL (120-mL bottle)
imipramine	Tofranil	Tablets: 10, 25, 50 mg	150–300
imipramine pamoate	Tofranil-PMf	Capsules: 75, 100, 125, 150 mg	150–300
nortriptyline	Aventyl, Pamelor	Capsules: 10, 25, 50, 75 mg	50–150
		Oral solution: 10 mg/5 mL (480-mL bottle)
protriptyline	Vivactil	Tablets: 5, 10 mg	15–60
trimipramine maleate	Surmontil	Capsules: 25, 50, 100 mg	150–300
D: TETRACYCLICS
amoxapine	Asendin	Tablets: 25, 50, 100, 150 mg	150–400
maprotiline	Ludiomil	Tablets: 25, 50, 75 mg	150–225

GENERIC NAME	BRAND NAME	TABLETS AND CAPSULES	ORAL CONCENTRATE	Usual Therapeutic Dosage (mg/day)b
E: MAOIS
phenelzine	Nardil	Tablet: 15 mg	None	45–90
selegiline	Eldepryl	Capsule: 5 mg	None	20–50
	Carbex	Tablet: 5 mg
	Zelapar	Orally disintegrating tablet: 1.25 mg
	Emsam	Patch: 6 mg/24 hr, 9 mg/24 hr, 12 mg/24 hr
tranylcypromine	Parnate	Tablet: 10 mg	None	30–60
isocarboxazid	Marplan	Tablet: 10 mg	None	30–60

Note: 5-HT₂ = serotonin₂ receptor.

^aAll the tricyclic and tetracyclic antidepressants shown are available generically. Most of the brand name drugs listed have been discontinued.

^bNot available in an injectable form.

^cDosage ranges are approximate. Many patients will respond at relatively low dosages (even dosages below those in ranges given above); others may require higher dosages.

^dTrazodone also available in 150- and 300-mg divided-dose formulations.

^eApproved for fibromyalgia; doses given are those recommended for that use.

^fSustained release.

Table 3. Pharmacokinetics of Selective Serotonin Reuptake Inhibitors (SSRIs).

SSRI	HALF-LIFE (HOURS)	METABOLITE AND ITS HALF-LIFE	PEAK PLASMA LEVEL (HOURS)	% PROTEIN BOUND
fluoxetine	24–72	norfluoxetine, 7–14 days	6–8	94
sertraline	25	N-desmethylsertraline, 2–3 days	6–8	95
paroxetine	<20	NA	2–8	99
fluvoxamine	15	NA	2–8	77
citalopram	35	NA	4–6	91
escitalopram	32	S-demethylcitalopram	5	56

Note: NA = not applicable.

Table 4. Adjunctive Agents for Selective Serotonin Reuptake Inhibitor (SSRI)–Induced Sexual Dysfunction.

ADJUNCTIVE AGENT	DOSAGE	STUDIES
buspirone	20–60 mg/day	Landén et al. 1999; Norden 1994
bupropion	75–150 mg/day	Ashton and Rosen 1998; Labbate and Pollack 1994; DeBattista et al. 2005
sildenafil	50–100 mg prn	Ashton and Bennett 1999; Gupta et al. 1999; Nurnberg et al. 1999a, 1999b, 2008; Fava et al. 2006a
tadalafil	10–20 mg	Segraves et al. 2007
vardenafil	10–20 mg	Rosen et al. 2006
Ginkgo biloba	60–240 mg/day	Wheatley 2004
amantadine	100–300 mg/day	Balon 1996; Shrivastava et al. 1995
cyproheptadine	4–12 mg prn	Aizenberg et al. 1995; Keller Ashton et al. 1997
yohimbine	5.4 mg tid	Jacobsen 1992; Price and Grunhaus 1990

Table 5. Inhibition of Cytochrome P450 Enzymes by Antidepressants.

ENZYME	DRUGS METABOLIZED	ANTIDEPRESSANT INHIBITORS
2D6	TCAs (hydroxylation)	fluoxetine (norfluoxetine)
	bupropion	sertraline (desmethylsertraline)
	venlafaxine	paroxetine
	thioridazine	fluvoxamine and citalopram (weakest)
	1C antiarrhythmics
	β-blockers
	paroxetine
	risperidone
	codeine
	haloperidol
	clozapine
	benztropine
	perphenazine
1A2	caffeine	fluvoxamine
	theophylline
	phenacetin
	TCAs (demethylation)
	clozapine
	diazepam
3A3/4	alprazolam	fluoxetine
	triazolam	sertraline
	TCAs (demethylation)	fluvoxamine
	terfenadine	nefazodone
	astemizole
	carbamazepine
	erythromycin
	dexamethasone
	citalopram
	escitalopram
	cyclosporine
2C19	TCAs (demethylation)	fluoxetine
	warfarin	fluvoxamine
	tolbutamide	sertraline
	phenytoin
	diazepam

Note: TCA = tricyclic antidepressant.

Table 6. Norepinephrine (NE) and Serotonin (5-HT) Reuptake–Blocking Effects of the Non-MAOI Antidepressants.

ANTIDEPRESSANT	NE	5-HT
amitriptyline	+	++
amoxapine	++	+
bupropion	+/–	0
citalopram/escitalopram	0	+++
clomipramine	++	+++
desipramine	+++	+
doxepin	+	+
fluoxetine	0	+++
fluvoxamine	0	+++
imipramine	+	++
levomilnacipran	++
maprotiline	++	0
mirtazapine	+	−
nefazodone	0/+	+
nortriptyline	++	+
paroxetine	+a	+++
protriptyline	+++	+
sertraline	0	+++
trazodone	0	+
trimipramine	0	0
venlafaxine	+	++

Note: Data are approximations of relative activity from in vivo, in vitro, and clinical studies. Data on clomipramine include results on desmethylclomipramine on both active metabolites with pronounced effects on horadrenergic systems. In certain in vivo models, the tricyclic antidepressants (other than clomipramine) and trazodone have been reported not to block 5-HT uptake. MAOI = monoamine oxidase inhibitor. Strength of effect represented on a scale from 0 (no effect) to +++ (marked effect). +/− indicates marginal effect.

^aEffect at high doses.

Table 7. Relative Receptor-Blocking Effects of Antidepressants.

ANTIDEPRESSANT	ACH	?1	H1	5-HT1	5-HT2
amitriptyline	+++	+++	++	+/–	+/–
amoxapine	+	++	+	+/–	+++
bupropion	0	0	0	0	0
citalopram/escitalopram	0	0	0	0	0
clomipramine	+	++	+	0	+
desipramine	+	+	+	0	+/–
doxepin	++	+++	+++	+/–	+/–
fluoxetine	0	0	0	0	+/–
fluvoxamine	0	0	0	0	0
imipramine	++	+	+	0	+/–
maprotiline	+	+	++	0	+/–
mirtazapine	0	0	+++	+	+
nefazodone	0	+	0	+	++
nortriptyline	+	+	+	+/–	+
paroxetine	+	0	0	0	0
protriptyline	+++	+	+	0	+
sertraline	0	0	0	0	0
trazodone	0	++	+/–	+	++
trimipramine	++	++	+++	0	+/–
venlafaxine	0	0	0	0	0

Note: Data are approximations of relative activity from in vivo, in vitro, and clinical studies.

ACh = muscarinic acetylcholine receptor; α₁ = α₁-adrenergic receptor, H₁ = histamine₁ receptor; 5-HT₁ = serotonin₁ receptor; 5-HT₂ = serotonin₂ receptor. Strength of effect represented on scale from 0 (no effect) to +++ (marked effect). +/– indicates marginal effect.

Table 8. Tricyclic Antidepressants (TCAs): Overview.

Efficacy	Second- or third-line agents for MDD (FDA approved for all)
	Panic disorder
	OCD (FDA approved for clomipramine)
	Pain syndromes
	Migraine prophylaxis
	Enuresis (FDA approved for imipramine)
Side effects	Dry mouth, constipation, urinary retention, blurred vision, confusion
	Weight gain
	Sedation
	Sexual dysfunction
	Orthostasis
	Tachycardia
	Cardiac conduction abnormalities
Dosage and administration	Individualize with low hs dosing (25–50 mg) for imipramine and amitriptyline. Increase by 25–50 mg every 3–7 days to target dosage of 150–300 mg/day. (Nortriptyline should be started at 10–25 mg and increased, as needed, to a maximum dosage of 150 mg/day.) Monitor levels and ECGs after dose stabilized.
Safety in overdose	Lethal in overdose (induces arrhythmias).
	Lavage and monitor on a cardiac bed for QRS widening.
Discontinuation	Flulike and GI symptoms from cholinergic rebound.
	Reduce by 25–50 mg every 3 days.
Drug interactions	CNS depressants: ↑ sedation, ataxia
	Anticoagulants: ↑ warfarin levels
	Antipsychotics: ↑ TCA and antipsychotic levels
	Cimetidine: ↑ TCA levels
	Clonidine: hypertensive crisis (avoid)
	l-Dopa: TCAs ↓ absorption
	MAOIs: serotonin syndrome (avoid clomipramine; imipramine and amitriptyline may be used with close monitoring)
	Stimulants: ↑ TCA levels
	Oral contraceptives: ↑ TCA levels
	Quinidine: ↑ arrhythmias (avoid)
	SSRls: ↑ TCA levels
	Sympathomimetics: ↑ arrhythmias, hypertension, tachycardia

Note: CNS = central nervous system; ECG = electrocardiogram; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; MAOI = monoamine oxidase inhibitor; MDD = major depressive disorder; OCD =obsessive-compulsive disorder; SSRI = selective serotonin reuptake inhibitor.

Table 9. Monoamine Oxidase Inhibitors (MAOIs): Overview.

Efficacy	Third-line agents for MDD (FDA approved for resistant depression)
	Social anxiety
	Panic disorder
	Second-line agents for Parkinson’s disease (selegiline has FDA approval)
Side effects	Weight gain
	Orthostasis
	Sexual dysfunction
	Dry mouth
	Insomnia/somnolence
	Headache
Safety in overdose	Can be lethal in overdose. Hypertensive crisis, stroke, and myocardial infarction have been reported. Manage with lavage, emesis induction, and close management of blood pressure and airway.
Dosage and administration	Phenelzine: start at 15 mg bid or tid and increase by 15 mg per week to target dosage of 60–90 mg/day.
	Tranylcypromine: start at 10 mg bid or tid and increase by 10 mg per week to target dosage of 40–60 mg/day.
	Isocarboxazid: start at 10 mg bid and increase dosage, if the drug is tolerated, by 10 mg every 2–4 days to 40 mg/day by end of first week. Maximum recommended dosage is 60 mg/day, administered in divided doses.
	Selegiline transdermal system (Emsam): start with 6-mg patch daily for 4 weeks and then increase to 9-mg patch for 2 weeks, and then 12-mg patch as needed. No dietary restrictions at 6 mg/day.
Discontinuation	Flulike symptoms, hallucinations, hypomania, and dysphoria reported with sudden discontinuation. Taper dose by 25% per week.
Drug interactions	Foods containing high levels of tyramine (contraindicated) (see Table 3–14): hypertensive crisis
	β-Blockers: ↑ hypotension, bradycardia
	Oral hypoglycemics: ↑ hypoglycemic effects
	Bupropion (contraindicated): hypertensive crisis, seizure
	Carbamazepine (contraindicated): hypertensive crisis
	Meperidine (contraindicated): serotonin syndrome
	Nefazodone: possible serotonin syndrome
	Sympathomimetics: hypertensive crisis
	SSRls (contraindicated): serotonin syndrome
	TCAs: clomipramine contraindicated
	Mirtazapine (contraindicated): hypertensive crisis
	SNRIs (contraindicated): serotonin syndrome

Note: FDA = U.S. Food and Drug Administration; MDD = major depressive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.

Table 10. Foods to be Avoided with Monoamine Oxidase Inhibitors (MAOIs).

Foods definitely to be avoided:

Beer, red wine

Aged cheeses (cottage and cream cheese are allowed)

Dry sausage

Fava or Italian green beans

Brewer’s yeast

Smoked fish

Liver (beef or chicken)

Foods that may cause problems in large amounts but are otherwise less problematic:

Alcohol

Ripe avocado

Yogurt

Bananas (ripe)

Soy sauce

Foods that were thought to be problems but are probably not problematic in usual quantities:

Chocolate

Figs

Meat tenderizers

Caffeine-containing beverages

Raisins

Source: Based on McCabe and Tsuang 1982.

Table 11. Antidepressant Overdoses and Their Management.

DRUG	TOXIC DOSE	TOXICITY MANIFESTATIONS	MANAGEMENT
TCAs	>1,500 mg (imipramine and most TCAs)	Anticholinergic symptoms, arrhythmia, hypotension, delirium, seizures	Gastric lavage, fluid support, cardiac monitoring
MAOIs	≥2 mg/kg	CNS excitation, hypo- or hypertension, delirium, fever, arrhythmia, seizures, rhabdomyolysis	Gastric lavage, fluids, cardiac monitoring, antihypertensives, body cooling, benzodiazepines for CNS symptoms, maintenance of MAOI diet
Bupropion	>2 g	CNS excitation, seizures	Gastric lavage, benzodiazepines, anticonvulsants
SSRIs	Unknown	CNS excitation, somnolence, GI irritation	Gastric lavage, supportive care
SNRIs (venlafaxine, duloxetine)	Unknown	Cardiotoxicity, hypertension, seizures, serotonin effects	Gastric lavage, supportive care

Note: CNS = central nervous system; G1 = gastrointestinal; MAOI = monoamine oxidase inhibitor; SNR1 = serotonin-norepinephrine reuptake inhibitor, SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.

Table 12. Potential Augmenting Agents for Antidepressants.

ANTIDEPRESSANT	AUGMENTING AGENT
Tricyclics/tetracyclics	lithium
	thyroid supplements
	amphetamines
	SSRIs
	monoamine precursors
	MAOIs
SSRIs	lithium
	thyroid supplements
	TCAs
	trazodone
	buspirone
	pindolol
	modafinil
	stimulants
	atomoxetine/reboxetine
	SGAs
	folate
	pramipexole/ropinirole
	mirtazapine
	bupropion
	lamotrigine
	d-cycloserine
MAOIs	lithium
	SGAs
	thyroid supplements
	TCAs

Note: SGA = second-generation antipsychotic; SSRI = selective serotonin reuptake inhibitor; MAOI = monoamine oxidase inhibitor; TCA = tricyclic antidepressant.

Table 13. Common Antidepressant Dosages in Children.

DRUG	DOSAGE RANGE	SERUM LEVEL (NG/ML)
imipramine	1–5 mg/kg/day	150–250
desipramine	1–5 mg/kg/day	150–250
nortriptyline	0.5–2 mg/kg/day	75–150
phenelzine	0.25–1 mg/kg/day	NA
fluoxetine	5–30 mg/day	NA
bupropion	1–7 mg/kg/day	NA
citalopram	10–20 mg/day	NA

Note: NA = not applicable.

Table 14. Mood Stabilizers: Names, Formulations, and Strengths.

GENERIC NAME	BRAND NAME	FORMULATIONS AND STRENGTHS
lithium carbonatea	Eskalith*	Capsule: 150, 300, 600 mg
	Lithobid (slow release)	Tablet: 300 mg
	Eskalith-CR* (controlled release)	Tablet: 450 mgb
lithium citrate	Genericc	Syrup: 8 mEq/5 mLd (480-mL bottle)
carbamazepinea	Tegretol	Tablets: 200 mg
		Chewable tablet: 100, 200 mg
		Suspension: 100 mg/5 mL (450-mL bottle)
	Tegretol-XR (sustained release)	Tablets: 100, 200, 400 mg
	Carbatrol (sustained release)	Capsules: 100, 200, 300 mg
valproic acida	Depakene	Capsule: 250 mg
		Syrup: 250 mg/5 mL (480-mL bottle)
valproate sodium	Depacon	Injection: 100 mg/mL (5-mL vial)
divalproex sodiuma	Depakote	Enteric-coated tablets: 125, 250, 500 mg Capsule, sprinkle: 125 mg
	Depakote ER (sustained release)	Tablets: 250, 500 mg
lamotriginea	Lamictale	Chewable tablets: 2, 5, 25 mg Tablets: 25, 100, 150, 200, 250 mg
	Lamictal ODTe	Orally disintegrating tablets: 25, 50, 100, 200 mg
	Lamictal XRe (extended release) and generic	Tablets: 25, 50, 100, 150, 200, 250, 300 mg
gabapentina,f	Neurontin	Capsules: 100, 300, 400 mg
		Tablets: 100, 300, 400, 600, 800 mg
		Oral solution: 250 mg/5 mL
	Gralise (extended release)	Tablets: 300, 600 mg
gabapentin enacarbif	Horizant (extended release)	Tablets: 300, 600 mg
oxcarbazepinea,f	Trileptal	Tablets: 150, 300, 600 mg
		Suspension: 300 mg/5 mL
	Oxtellar XR (extended release)	Tablets: 150, 300, 600 mg
topiramatea,f	Topamax	Tablets: 25, 50, 100, 200 mg
		Capsules, sprinkle: 15, 25 mg
	Qudexy XR	Capsules, sprinkle: 25, 50, 100, 150, 200 mg
	Trokendi XR	Capsules: 25, 50, 100, 200 mg
tiagabinea,f	Gabitril	Tablets: 2, 4, 12, 16 mg

^aAvailable in generic form.

^bScored tablets.

^cCibalith-S: brand discontinued.

^dEquivalent to 300 mg lithium carbonate.

^ePatient titration kits available.

^fNot FDA approved for mood stabilization or for other psychiatric uses.

*Brand taken off the market; available in generic.

Table 15. New Anticonvulsants.

	PREGABALIN (LYRICA)	OXCARBAZEPINE (TRILEPTAL)	GABAPENTIN (NEURONTIN)	LAMOTRIGINE (LAMICTAL)	TOPIRAMATE (TOPAMAX)	TIAGABINE (GABITRIL)
Serum plasma level, ng/mL	NA	NA	NA	NA	NA	1–234
Adult dosage, mg/day	150–600	600–2,400	900–2,400 (for seizure maintenance treatment)	300–500 (for seizure maintenance treatment)	200–400 (for seizure maintenance treatment)	4–32
	300–450 given in divided doses (for fibro-myalgia)			200 (for bipolar disorder monotherapy)	100 given in two divided doses (for migraine prophylaxis)
	150–300 given in divided doses (for neuropathic pain)			100 (concurrently with valproate for bipolar disorder)
				400 (concurrently with carbamazepine or other enzyme-inducing drugs [and not taking valproate] for bipolar disorder)
Protein binding	–	40% bound	Minimally bound (<3%)	55% bound	20% bound	96% bound
Half-life, hours	–	2–9	5–7	25–32	20–30	7–9
Metabolic pathway	–	Hepatic CYP 3A enzyme	Drug not appreciably metabolized hepatically	Glucuronidation/conjugation	20% metabolized hepatically	Oxidation/glucuron-idation
Routes of elimination	–	Renal (95%); fecal (5%)	Renal	Renal	Renal	Urinary (25%); fecal (63%)
Common drug interactions	No significant drug interactions are known; antacids decrease absorption and bioavailability of pregabalin	Induces metabolism of CYP 3A3/4– dependent drugs (weaker than carba-mazepine); decreases levels of pheno-barbital, phenytoin, sex steroids, haloperidol, valproic acid, calcium channel blockers, and others (see Table 5–4)	No significant drug inter-actions are known; antacids decrease bio- availability of gabapentin by 20%; cimetidine decreases renal clearance by 13%	Valproate doubles serum levels; carbamazepine decreases serum levels by 50%; phenytoin decreases serum levels by 50%	Phenobarbital decreases serum levels by 40%; carbamazepine decreases topi-ramate levels by 50%–60%; valproate decreases topiramate levels by 15%; phenytoin decreases topiramate levels by 48%	Carbamaze-pine decreases tiagabine levels; phenytoin decreases tiagabine levels; tiagabine decreases valproate levels
Common adverse effects	Somnolence, dizziness, ataxia, fatigue	Dizziness, drowsiness, ataxia, weight gain	Somnolence, dizziness, fatigue, ataxia	Rash: 1 of 10 (serious rashes, such as Stevens-Johnson syndrome: 1 of 1,000), dizziness, ataxia, nausea, vomiting	Psychomotor slowing, decreased concentration, somnolence, fatigue, anorexia, kidney stone formation	Dizziness, depression, asthenia, nervousness, tremors, somnolence, cognitive deficits
Indication (FDA approved)	Partial seizures	Partial complex seizures	Partial seizures	Partial seizures	Epilepsy	Epilepsy
	Postherpetic neuralgia		Postherpetic neuralgia	Maintenance treatment of bipolar I disorder	Prophylaxis of migraine headaches
	Fibromyalgia
	Neuropathic pain associated with diabetic neuropathy

Note: CYP = cytochrome PH50; FDA = U.S. Food and Drug Administration; NA = not applicable.

Source. Adapted for the most part from 2002 black book.

Table 16. Toxicology of Mood Stabilizers.

SYSTEM	LITHIUM	DRUG VALPROATE	CBZ	GABAPENTIN	LAMOTRIGINE	TOPIRAMATE	TIAGABINE
CNS	Tremor	Sedation	Sedation	Somnolence	Dizziness	Dizziness	Dizziness
	Ataxia	Tremor	Dizziness	Dizziness	Ataxia	Ataxia	Somnolence
	Cognitive slowing	Ataxia	Ataxia	Ataxia	Somnolence	Speech problems	Difficulty concentrating
						Cognitive slowing
GI	Dyspepsia	Dyspepsia	Dyspepsia	Dyspepsia (rare)	Nausea	Nausea	Nausea
	Weight gain	LFT increases	LFT increases		Vomiting	Dyspepsia	Abdominal pain
	Diarrhea	Weight gain				Abdominal pain
		Hepatic failure (rare)
		Pancreatitis
Dermatological	Rash	Rash	Rash	Pruritus (rare)	Rash	Rash (rare)	Rash (rare)
	Hair loss	Hair loss			Acne	Pruritis (rare)	Alopecia
	Acne
Renal/Urogenital	NDI	Minimal	SIADH	None	Vaginitis	Dysmenor-rhea	None
	Nephropathy				Urinary tract infection	Metabolic acidosisa
Cardiac	T wave changes	Minimal	Arrhythmia	None	Palpitations (rare)	BP changes (rare)	Hypertension
	Sinoatrial block				Hypotension (rare)		Palpitations
Hematological	Leukocytosis	Thrombo-cytopenia	Thrombo-cytopenia	Leukopenia (rare)	None	Leukopenia	None
		Coagulation defect	Aplastic anemia (rare)
Endocrine	Hypothyroidism	Minimal	Lower levels of T3, T4	None	Hypothyroidism (rare)	Weight decrease	Goiter (rare)

Note: 8P = blood pressure; CBZ = carbamazepine; CNS = central nervous system; GI = gastrointestinal; LFT = liver function test; NDI = nephrogenic diabetes insipidus; SIADH = syndrome of inappropriate antidiuretic hormone; T₃ = triiodothyronine; T₄ = thyroxine.

^aSecondary to hyperchloremia.

Table 17. Anticonvulsant Dosages in Bipolar Illness.

MEDICATION	USUAL DOSAGE RANGE	SERUM LEVEL (μG/ML)
valproate	15–60 mg/kg/day	50–125
carbamazepine	200–1,600 mg/day	6–10
lamotrigine	50–200 mg/day	NA
gabapentin	900–3,600 mg/day	NA
oxcarbazepine	600–2,400 mg/day	NA

Note: NA = not applicable.

Table 18. Drug Interactions of Anticonvulsant Mood Stabilizers.

ANTICONVULSANT	DRUGS THAT MAY ↑ ANTICONVULSANT LEVELS	DRUGS THAT MAY ↓ ANTICONVULSANT LEVELS	DRUGS WHOSE BLOOD LEVELS ↓ WITH CONCURRENT ANTICONVULSANT USE
Valproate	Aspirin	Carbamazepine	Zonisamide
	Cimetidine	Ethosuximide	Clinically significant metabolic induction by other drugs with valproate not reported
	Clarithromycin	Oxcarbazepine
	Erythromycin	Phenobarbital
	Fluvoxamine	Phenytoin
	Fluoxetine	Primidone
	Ibuprofen	Rifampin
	Phenothiazines
	Topiramate
	Troleandomycin
Carbamazepine	Cimetidine	Felbamate	Atypical antipsychotics
	Ciprofloxacin	Phenobarbital	Benzodiazepines
	Clarithromycin	Rifampin	Doxycycline
	Diltiazem		Ethosuximide
	Doxycycline		Fentanyl
	Erythromycin		Glucocorticoids
	Fluconazole		Methadone
	Fluoxetine		Neuroleptics
	Fluvoxamine		Oral contraceptives
	Grapefruit juice		Phenytoin
	Isoniazid		Protease inhibitors
	Itraconazole		TCAs (?)
	Ketoconazole		Theophylline
	Nefazodone
	Norfloxacin
	Prednisolone
	Propoxyphene
	Protease inhibitors (e.g., Ritonavir, Indinavir)
	TCAs
	Troleandomycin
	Valproate
	Verapamil
	Warfarin
Lamotrigine	Valproate	Carbamazepine	Valproate
		Ethosuximide oral Contraceptives
		Oxcarbazepine
		Phenobarbital
		Phenytoin
		Primidone
Oxcarbazepine			Ethinyl estradiol levonorgestrel
Topiramate			Oral contraceptives

Note: TCAs = tricyclic antidepressants; ↑ = increase; ↓ = decrease.

Table 19. Common Mood Stabilizer Dosages in Children.

DRUG	DOSAGE RANGE	SERUM LEVEL
lithium	300–2,400 mg/day	0.5–1.2 mEq/L
valproate	15–60 mg/kg/day	50–100 μg/mL
carbamazepine	10–50 mg/kg/day	8–12 μg/mL
oxcarbazepine	5–30 mg/kg/day (150–1,200 mg/day)	NA
Iamotrigine	0.15–5.0 mg/kg/day (25–200 mg/day)	NA

Table 20. Antipsychotic Drugs: Names, Formulations, and Strengths.

GENERIC NAME	BRAND NAME	FORMULATIONS AND STRENGTHS
Aripiprazole	Abilify	Tablets: 2, 5, 10, 15, 20, 30 mg
	Abilify disc melt	Orally disintegrating tablets: 10, 15 mg
		Oral solution: 1 mg/mL (150 mL)
		Injection: 9.75 mg/1.3 mL
	Abilify maintena	Intramuscular injection: 300, 400 mg
Asenapine	Saphris	Tablets (sublingual): 5, 10 mg
Chlorpromazine	Thorazinea	Tablets: 10, 25, 50, 100, 200 mg
		Injection: 25 mg/mL (1-mL and 2-mL ampules)
Clozapine	Clozarila,b	Tablets: 25, 50, 100, 200 mg
		Oral suspension: 50 mg/mL
	FazaClo	Orally disintegrating tablets: 12.5, 25, 50, 100, 150, 200 mg
Droperidol	Inapsinea	Injection: 2.5 mg/mL (1- and 2-mL ampules and vials)
Fluphenazine	Prolixina	Tablets: 1, 2.5, 5, 10 mg
		Concentrate: 5 mg/mL (120-mL bottle)
		Elixir: 2.5 mg/5 mL (60-mL and 473-mL bottles)
		Injection: 2.5 mg/mL (10-mL multidose vial)
Fluphenazine decanoate	Prolixin decanoatea	Injection: 25 mg/mL (5-mL multidose vial)
Haloperidol	Haldola	Tablets: 0.5, 1, 2, 5, 10, 20 mg
		Concentrate: 2 mg/mL
		Injection: 5 mg/mL (1-mL ampule and single-dose vial; 10-mL multidose vial)
Haloperidol decanoate	Haldol decanoatea	Injection: 50 mg/mL (1-mL ampule and 5-mL multidose vial), 100 mg/mL (5-mL multidose vial)
Iloperidone	Fanapt	Tablets: 1, 2, 4, 6, 8, 10, 12 mg
Loxapine	Loxitanea	Capsules: 5, 10, 25, 50 mg
	Adasuve	Inhalation powder: 10-mg unit in single-use inhaler; must be administered by health care professional
Lurasidone	Latuda	Tablets: 20, 40, 60, 80, 120 mg
Olanzapine	Zyprexaa	Tablets: 2.5, 5, 7.5, 10, 15, 20 mg
	Zydisa	Orally disintegrating tablets: 5, 10, 15, 20 mg
	Zyprexa intramuscular	Injection: 10-mg vial (before reconstitution)
Paliperidone	Invega	Tablets (extended release): 1.5, 3, 6, 9 mg
Paliperidone palmitate	Invega Sustenna	Injection: 39, 78, 117, 156, 234 mg
Perphenazine	Trilafona	Tablets: 2, 4, 8, 16 mg
Pimozide	Orap	Tablets: 1, 2 mg
Quetiapine	Seroquela	Tablets: 25, 50, 100, 200, 300, 400 mg
	Seroquel XR	Tablets (extended release): 50, 150, 200, 300, 400 mg
Risperidone	Risperdala	Tablets: 0.25, 0.5, 1, 2, 3, 4 mg
		Oral solution: 1 mg/mL (30-mL bottle)
	Risperdal M-TABa	Orally disintegrating tablets: 0.5, 1, 2, 3, 4 mg
	Risperdal Consta	Long-acting injectable: 12.5, 25, 37.5, 50 mg
Thioridazine	Mellarila	Tablets: 10, 25, 50, 100 mg
		Concentrate: 30 mg/mL (120-mL bottle)
Thiothixene	Navanea	Capsules: 1, 2, 5, 10 mg
Trifluoperazine	Stelazinea	Tablets: 1, 2, 5, 10 mg
Ziprasidone	Geodona	Tablets: 20, 40, 60, 80 mg
		Injection: 20-mg vial (before reconstitution)

^aAvailable in generic form.

^bUse of clozapine must be registered with the manufacturer’s monitoring national registry (see subsection “Clozapine” in this chapter).

Table 21. Antipsychotic Drug Potency.

GENERIC NAME	BRAND NAME	CHLORPROMAZINE EQUIVALENCE
aripiprazole	Abilify	10 mg
chlorpromazine	Thorazine	100 mg
clozapine	Clozaril	50 mg
fluphenazine	Prolixin	2 mg
hydrochloride
fluphenazine	Prolixin	0.25 cc/month
decanoate	Decanoate
haloperidol	Haldol	2 mg
loxapine	Loxitane	10 mg
molindone	Moban	10 mg
olanzapine	Zyprexa	~5 mg
perphenazine	Trilafon	10 mg
prochlorperazine	Compazine	15 mg
quetiapine	Seroquel	63 mg
risperidone	Risperdal	0.5 mg
thioridazine	Mellaril	100 mg
thiothixene	Navane	4 mg
trifluoperazine	Stelazine	5 mg

Table 22. Typical (D₂ Antagonist) Antipsychotics: Overview.

Efficacy	Schizophrenia (positive symptoms) (FDA-approved indication)
	Tourette’s disorder (pimozide; FDA-approved indication)
	Mania (FDA-approved indication for chlorpromazine only)
	Psychotic depression (with antidepressant)
	Drug-induced psychosis
	Agitation,a nausea, hiccups (not FDA approved for these purposes; off-label)
Side effects	EPS (more common in high-potency drugs)
	NMS (rare)
	Dry mouth, constipation, urinary retention, sedation, weight gain (more common in low-potency drugs)
	Skin and eye complications QT interval prolongation (thioridazine)
Dosage and administration	Individualize dosing.
	50–150 mg chlorpromazine equivalents (see Table 4–2) to start, with maximum total daily dose of 300–600 mg chlorpromazine equivalents (e.g., 6–12 mg haloperidol).
Safety in overdose	CNS depression, hypotension, ECG changes, EPS. Manage with vital sign support, gastric lavage. Do not induce emesis secondary to aspiration risk.
Drug interactions	CNS depressants: ↑ sedation
	Antacids: ↓ antipsychotic absorption
	Carbamazepine: ↓ antipsychotic levels
	SSRIs: ↑ antipsychotic levels
	Nicotine: ↓ antipsychotic levels
	Meperidine: ↑ sedation, hypotension
	β-Blockers: ↑ hypotension; may ↑ antipsychotic and β -blocker levels
	TCAs: may ↑ antipsychotic and TCA levels
	Valproic acid: chlorpromazine may ↑ valproic acid levels

Note: CNS = central nervous system; ECG = electrocardiogram; EPS = extrapyramidal symptoms; FDA = U.S. Food and Drug Administration; NMS = neuroleptic malignant syndrome; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.

^aAgitation associated with psychosis: FDA-approved indication for intramuscular olanzapine only.

Table 23. Second-Generation (Dopamine-Serotonin Antagonist) Antipsychotics: Overview.

Efficacy	Schizophrenia (FDA approved for all)
	Treatment-resistant schizophrenia (clozapine)
	Mania (FDA approved for aripiprazole, asenapine, olanzapine, quetiapine, risperidone, and ziprasidone)
	Bipolar depression (FDA approved for lurasidone, quetiapine, and Symbyax [olanzapine-fluoxetine])
	Depression/anxiety/agitation (efficacy established but not FDA approved for these purposes)
Side effects	Weight gain
	Gastrointestinal effects
	Insulin resistance
	Sedation
	Akathisia
	Orthostatic hypotension
	Bradykinesia
	Tachycardia
	Dizziness
	↑ Triglycerides (except ziprasidone)
	EPS, NMS (rare)
	Agranulocytosis (clozapine) (rare)
	Seizures (clozapine)
Safety in overdose	Seizures with clozapine in overdose. Respiratory depression in combination with other CNS depressants. QT interval changes. Lavage and vital sign support.
Dosage and administration	Clozapine: 12.5–25 mg; then increase dosage 25–50 mg per week, as needed and tolerated, to 300–600 mg/day
	Risperidone: 0.5–1 mg bid to 3 mg bid by end of first week, as tolerated
	Olanzapine: 2.5–5 mg hs; increase by 5 mg every week to 20 mg hs
	Quetiapine: 25 mg bid; increase total daily dose by 50 mg, as needed and tolerated, to 300–600 mg/day
	Ziprasidone: 20 mg qd or bid; increase by 20–40 mg per week, to a maximum dosage of 80 mg bid
	Aripiprazole: 15 mg qd; increase up to 30 mg/day after 1 week
	Lurasidone: 20–40 mg/day; increase by 20–40 mg/day up to 120–160 mg/day
	Asenapine: 5–10 mg bid sublingually and then increase by 5 mg/day to a maximum of 10 mg bid
	Iloperidone: 1 mg po bid day one, 2 mg bid day two, and then increase by 2 mg/day to a target dosage of 6–12 mg/day
FULL BENEFITS IN 4 WEEKS TO 6 MONTHS
Discontinuation	Mild cholinergic rebound, faster relapse. Taper as slowly as titrated up.
Drug interactions	Fluvoxamine (1A2 inhibitor): ↑ second-generation antipsychotic levels
	EtOH: ↑ sedation and orthostasis
	Antihypertensives: may ↑ orthostasis
	Carbamazepine: ↓ serum levels of olanzapine; ↓ clozapine levels; ↑ hematological adverse events with clozapine
	CNS depressants: ↑ sedation
	Ciprofloxacin (Cipro) (potent 1A2 inhibitor): ↑ second- generation antipsychotic levels

Note: CNS = central nervous system; EPS = extrapyramidal symptoms; EtOH = ethanol; FDA = U.S. Food and Drug Administration; NMS = neuroleptic malignant syndrome.

Table 24. Antipsychotic Dosages in Children.

DRUG	COMMON PEDIATRIC THERAPEUTIC DOSAGE
Chlorpromazine	0.25 mg/kg tid
Trifluoperazine	0.5–10 mg bid
Haloperidol	0.15–0.5 mg/kg/day (in divided doses [bid])
Aripiprazole	2–10 mg/day
Olanzapine	2.5–5 mg qhs
Quetiapine	25–300 mg/day
Risperidone	1–2 mg/day

Table 25. Antiparkinsonian Drugs: Names, Formulations, Strengths, and Dosage Ranges.

GENERICNAME	BRANDNAME	FORMULATIONS AND STRENGTHS	USUAL DOSAGE RANGE (MG/DAY)
Primarily	Cogentina	Tablets: 0.5, 1, 2 mg	2–6
anticholinergic		Injection: 1 mg/mL (2-mL ampule)
benztropine
Biperiden	Akineton	Tablet (HCI): 2 mg	2–8
Diphenhydramine	Benadrylb	Tablet: 25 mg	50–300
		Capsules: 25, 50 mg
		Elixir and syrup: 12.5 mg/5 mL (120-mL and 480-mL bottles)
		Injection: 50 mg/mL (1-mL single-dose vial; 10-mL multidose vial; 1-mL prefilled syringe)
Trihexyphenidyl	Artaneb	Tablets: 2, 5 mg	4–15
		Elixir: 2 mg/5 mL (480-mL bottle)
Dopaminergic amantadine	Symmetrelb	Tablet and capsule: 100 mg	100–300
		Syrup: 50 mg/5 mL (480-mL bottle)

^aTablets only available in generic form.

^bAvailable in generic form.

Table 26. Interactions of Commonly Used Psychoactive Drugs with Cardiovascular Medications.

DRUG	TCA	SSRI	ANTIPSYCHOTIC	LITHIUM	CARBAMAZEPINE
calcium channel blockers	Increase hypotension	NA	Increase hypotension	Raise or lower lithium levels, bradycardia	Increase carbamazepine levels
thiazide diuretics	May increase hypotension	NA	Increase hypotension	Increase lithium levels	NA
β-blockers	May increase hypotension	May increase β-blockers	Increase antipsychotic levels	NA	Decrease β-blocker levels
reserpine, guanethidine	Antagonize antihypertensive agents	NA	Increase hypotension	NA	Unknown
clonidine, prazosin	Increase hypotension	NA	Increase hypotension	NA	Unknown
1A antiarrhythmics	Prolong cardiac conduction	NA	Prolong cardiac conduction	Prolong sinus recovery time	May decrease antiarrhythmic levels
1C antiarrhythmics	Prolong cardiac conduction	Increase 1C levels	May prolong cardiac conduction	Prolong sinus recovery time	May decrease antiarrhythmic levels
digitalis	Increases digoxin and TCA levels	May increase digoxin levels	May increase digoxin levels	Prolongs sinus recovery time	Unknown

Note: NA = applicable; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.

Table 27. Benzodiazepines: Names, Formulations, Strengths, and Anxiolytic Dosage Range.

GENERIC NAME	BRAND NAMEa	FORMULATIONS AND STRENGTHS	ANXIOLYTIC DOSAGE RANGE (MG/DAY) b
2-KETO
chlordiazepoxide	Librium	Capsules: 5, 10, 25 mg	15–40
clorazepate	Tranxene	Tablets: 3.75, 7.5, 15 mg	15–40
diazepam	Valium	Tablets: 2, 5, 10 mg	5–40
		Oral solution: 1 mg/mL
		Concentrate solution: 5 mg/5 mL (30-mL)
		Injection: 5 mg/mL, 10 mg/2 mL intramuscular device injection
		Rectal gel: 2.5, 10, 20 mg
clonazepam	Klonopin	Tablets: 0.5, 1, 2 mg
		Oral disintegrating tablets: 0.125, 0.25, 0.5, 1, 2 mg
3-HYDROXY
lorazepam	Ativan	Tablets: 0.5, 1, 2 mg	1–6
		Oral concentrate: 2 mg/mL (30-mL)	1–2
		Injection: 2 mg/mL, 4 mg/mL (both in 1-mL prefilled syringe and single-dose vial and 10-mL multidose vial)
oxazepam	Serax	Capsules: 10, 15, 30 mg	15–120
TRIAZOLO
alprazolam	Xanax	Tablets: 0.25, 0.5, 1, 2 mg	1–4
		Oral disintegrating tablets: 0.25, 0.5, 1, 2 mg
		Oral concentrate: 1 mg/mL
alprazolam XR	Xanax XR	Tablets: 0.5, 1, 2, 3 mg

^aThe benzodiazepines shown are available in generic form.

^bApproximate dosage ranges. Some patients will require higher dosages; others may respond to dosages below the range.

Table 28. Benzodiazepines (e.g., Diazepam, Clonazepam, Alprazolam): Overview.

Efficacy	Generalized anxiety (FDA approved)
	Panic disorder (FDA approved for alprazolam, clonazepam)
	Insomnia (FDA approved)
	Seizure disorder (FDA approved for clonazepam)
	Muscle relaxation
	Anesthesia
	Alcohol withdrawal
Side effects	Sedation
	Lethargy
	Dependence/Withdrawal
Safety in overdose	Safe in overdose up to 30 times the normal daily dose. Usual symptoms of overdose include sedation, drowsiness, ataxia, and slurred speech. May result in respiratory depression in combination with other CNS depressants. Management includes gastric lavage, forced emesis, and assisted ventilation.
Dosage and administration	Varies by benzodiazepine and indication; see Table 6–1.
Discontinuation	Taper by no more than 25% of total dose per week after long-term administration. Withdrawal includes insomnia, agitation, anxiety, and, rarely, seizures.
Drug interactions	Additive CNS depression with ethanol, barbiturates, and other CNS depressants
	Drugs that ↑ triazolo-benzodiazepine levels include; cytochrome P450 3A4 inhibitors, ketoconazole, fluconazole, nefazodone
	Drugs that ↓ triazolo-benzodiazepine levels include: carbamazepine

Note: CNS = central nervous system; FDA = U.S. Food and Drug Administration.

Table 29. Benzodiazepines: Absorption and Pharmacokinetics.

GENERIC NAME	ORAL ABSORPTION	MAJOR ACTIVE COMPONENTS	APPROXIMATE HALF-LIFE (HOURS)a
2-KETO
chlordiazepoxide	Intermediate	chlordiazepoxide	20
		desmethylchlordiazepoxide	30
		demoxepam	Unknown
		desmethyldiazepam	60
clorazepate	Fast	desmethyldiazepam	60
diazepam	Fast	diazepam	40
		desmethyldiazepam	60
		methyloxazepam	10
halazepam	Intermediate	desmethyldiazepam	60
prazepam	Slow	desmethyldiazepam	60
3-HYDROXY
lorazepam	Intermediate	lorazepam	14
oxazepam	Slow to intermediate	oxazepam	9
TRIAZOLO
Alprazolam	Intermediate	alprazolam	14
alprazolam XR

^aBased on ranges of half-lives reported in young, psychiatrically and physically healthy volunteers.

Table 30. Benzodiazepine Hypnotics.

GENERIC NAME	BRAND NAME	FORMULATION AND STRENGTHS	DOSAGE (MG/DAY)	ABSORPTION	MAJOR ACTIVE METABOLITES	APPROXIMATE HALF-LIFE (HRS)
flurazepama	Dalmane	Capsules: 15, 30 mg	15–30	Intermediate	hydroxyethylflurazepam	1
					desalkylflurazepam	100
temazepama	Restoril	Capsules: 7.5, 15, 22.5, 30 mg	15–30	Intermediate	None	8
quazepam	Doral	Tablets: 15 mg	7.5–15	Intermediate	oxoquazepam	39
					desalkyloxoquazepam	73
triazolama	Halcion	Tablets: 0.125, 0.25 mg	0.125–0.5	Intermediate	—	3
estazolama	ProSom	Tablets: 1, 2 mg	1–4	Intermediate	—	16

^aAvailable in generic form.

Table 31. Other Nighttime Hypnotic Agents.

GENERIC NAME	BRAND NAME	FORMULATIONS AND STRENGTHS	DOSAGE (MG/DAY)a
zolpidem	Ambienb	Tablets: 5, 10 mg	5–10
	Ambien-CR	Tablets (extended release): 6.25, 12.5 mg
	Edular	Sublingual: 5, 10 mg
	Zolpimist	Oral spray solution: 5 mg/spray (60 mL)
zaleplon	Sonatab	Capsules: 5,10 mg	5–10
eszopiclone	Lunestab	Tablets: 1, 2, 3 mg	1–3
ramelteon	Rozerem	Tablet: 8 mg	8

^aAdult dosages. Patients may require slightly higher dosages of choloral hydrate or ethchlorvynol. For child dosages, consult the latest edition of Goodman & Gilman’s.

^bLower doses may be indicated when combined with potent cytochrome P450 3A4 inhibitors (e.g., fluoxetine).

Table 32. Anorexiants.

AGENT	DOSAGE RANGE (MG/DAY)	INDICATION
Lorcaserin (Belviq, Belviq XR)	20–40	Obesity
Naltrexone-Bupropion (Contrave)	16/180 bid	Obesity
Phendimetrazine (various)	70–105	Obesity
Phentermine-topiramate (Qsymia)	3.75/23–15/92	Obesity
Zonisamide (Zonegran, Excegran)	100–600	Obesity

Table 33. Stimulants: Names, Formulations, and Strengths.

GENERIC NAME	BRAND NAME	FORMULATIONS AND STRENGTHS
D-amphetaminea	Dexedrine Spansule (sustained release)	Capsules: 5, 10, 15 mg
	Immediate release	2.5, 7.5, 15, 20, 30 mg
amphetamine/dextroamphetaminea,b	Adderall	Tablets: 5, 7.5, 10, 12.5, 15,20, 30 mg
	Adderall XR	Capsules: 5, 10, 15, 20, 25, 30 mg
D-methamphetaminea	Desoxyn	Tablet: 5 mg
Methylphenidatea	Ritalin	Tablets: 5, 10, 20 mg
	Methylin	Tablets, chewable: 2.5, 5, 10 mg
		Oral solution: 5 mg/5 mL, 10 mg/5 mL (500 mL)
	Methylin ER	Tablets: 10, 20 mg
	Ritalin SR	Tablet: 20 mg
	Ritalin LA	Capsules: 10, 20, 30, 40 mg
	Metadate ER	Tablets: 20 mg
	Metadate CD	Capsules: 10, 20, 30, 40, 50, 60 mg
	Concerta	Tablets: 18, 27, 36, 54 mg
	Daytrana	Transdermal patch: 10, 15, 20, 30 mg/ 9 hoursc
dexmethylphenidatea,b	Focalin	Tablets: 2.5, 5, 10 mg
	Focalin XR	Capsules: 5, 10, 15, 20, 25, 30, 35, 40 mg
lisdexamfetamine	Vyvanse	Capsules: 20, 30, 40, 50, 60, 70 mg
modafinila	Provigil	Tablets: 100, 200 mg
armodafinil	Nuvigil	Tablets: 50, 150, 250 mg
guanfacine extended release	Intuniv	Tablets: 1, 2, 3, 4 mg

^aAvailable in generic form.

^bAvailable in generic except the extended-release form.

^cDelivery rate of 1.1, 1.6, 2.2, and 3.3 mg/hour for the 10-, 15-, 20-, and 30-mg patches, respectively. In vivo delivery rate is based on a wear period of 9 hours of pediatric patients ages 6–12 years.

Table 34. Drugs for Alzheimer’s Disease (Cholinesterase Inhibitors & Memantine).

DRUG	DOSAGE	PEAK PLASMA	ELIMINATION HALF-LIFE	STEADY STATE	PROTEIN BINDING	METABOLISM
Donepezil (Aricept)	5–10 mg/day	3–4 hours	70 hours	15 days	96%	2D6, 3A3/4
Galantamine (Reminyl)	16–32 mg/day	1 hour	7 hours	–	18%	2D6, 3A4
Memantine (Namenda, Namenda XR)	5–28 mg/day	3–7 hours	60–80 hours	12 weeks	45%	Not CYP dependent
Rivastigmine (Exelon)	6–12 mg/day	1.4–2.6 hours	1.5–3 hours	24–48 days	40%	Not CYP dependent
Tacrine (Cognex)	40–160 mg/day	1–2 hours	2–4 hours	24–36 hours	55%	1A2

CYP = cytochrome P450.

Table 35. Adverse Effects of Cholinesterase Inhibitors.

SYMPTOM	DONEPEZIL	GALANTAMINE	RIVASTIGMINE	TACRINE
GI
Nausea,	+	++++	++	+++
Vomiting
Weight loss	+	+	++ (dose dependent)	+
LFTs rise	−	−	−	+++
CNS
Insomnia	+/−	+	+/−	+
Fatigue	+/−	+	+/−	+/−
Depression	+/−	+	+/−	+/−
MISCELLANEOUS
Syncope	+/−	+	+	+/−
Increased urination	+/−	+	+/−	+/−
Rhinitis	+/−	+	−	−