Psychotropics cns 12.01

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					                           Review of
                      TALIA PUZANTIAN, PHARMD, BCPP
                            Clinical Pharmacist in Psychiatry
                             San Francisco General Hospital
                                     San Francisco, California

                      GLEN L. STIMMEL, PHARMD, FCCP
                   Professor of Clinical Pharmacy, Psychiatry
                                 and the Behavioral Sciences
                            University of Southern California
                          Schools of Pharmacy and Medicine
                                       Los Angeles, California

         sychopharmacology, in particular the introduc-          that for elderly patients, the daily doses are generally
         tion of new psychotropic agents, is perhaps the         lower than the adult doses listed here.
         most rapidly growing area in all of clinical phar-         In clinical medicine (as in the Tables), psychotropic
   macology. In recent years, important new drug intro-          medications are most usefully classified according to
   ductions have revolutionized the treatment of various         therapeutic applications, including:
psychiatric disorders. This progress has been made pos-          • anxiolytic agents for the treatment of
sible by advances in basic neuroscience and clinical                anxiety disorders;
research achieved during the past few decades. Recently          • antipsychotics for the treatment of schizophrenia;
introduced psychotropic drugs reflect an increased                  these drugs are sometimes referred to as neurolep-
understanding of the biological/biochemical mecha-                  tics because of characteristic side effects on cogni-
nisms of the psychiatric disorders they target. This                tion and behavior that mimic neurologic diseases
knowledge enables development of therapeutic agents                 (some newer, atypical antipsychotics demonstrate
with greater specificity for the molecular mechanisms in-           improved side-effect profiles);
volved, resulting in increased effectiveness and fewer           • drugs for mood (or affective) disorders, including
untoward side effects. Psychotropic drug development                antidepressants (mood-elevating agents) for the
continues at a rapid pace as the knowledge base of neu-             treatment of depression and mood-stabilizing agents
roscience and clinical research continues to expand. The            for the treatment of manic (or bipolar) disorders;
Tables that follow summarize the current state of the art           and
of psychotropic drugs available to clinicians. Please note       • hypnotics for the induction of sleep.

        C = capsule                                  IM = intramuscular                         OTC    = over the counter                 T = tablet
       DR = delayed release                           L = liquid                                 PO    = by mouth                     TCA = tricyclic antidepressant
      EPS = extrapyramidal side effects          MAOI = monoamine oxidase inhibitor             REM    = rapid eye movement              t 1⁄2 = half-life
                                                                                                  SR   = sustained release
       ER = extended release                       N/A = not available                                                                  tpk = time to peak
                                                                                                SSRI   = selective serotonin
        h = hour                                     NE = norepinephrine                                 reuptake inhibitor             XR = extended release
         I = injectable                            OCD = obsessive-compulsive disorder         SUPP = suppository                     5-HT = serotonin

                                                                                                                         CNS NEWS SPECIAL EDITION • DECEMBER 2001      13
                                                         Usual Adult                                    Relative Adverse-Effect Profiles
                                                  Dosage Daily Dosage                                          Orthostatic       Sexual           GI        Activation/
Class                      Agent                  Forms     (mg/d)          Anticholinergic      Sedation     Hypotension Dysfunction*          Effects      Insomnia           Comments
                       Amitriptyline                                                                                                                                      other common uses:
                                                   T, IM      100-300          very high         very high      very high         high         very low        none
                 Elavil, AstraZeneca; Others                                                                                                                              chronic pain, hypnotic

                                                                                                                                                                          approved for OCD;
                       Clomipramine                                                                                                                                       250 mg daily maximum
                                                      C       100-250          very high         very high      very high       very high      very low        none
               Anafranil, Mallinckrodt; Others                                                                                                                            due to increased risk of
                                                                                                                                                                                                       2,000 mg can
                                                                                                                                                                                                       be fatal in over-
                       Desipramine                                                                                                                                                                     dose in adults;
                                                    T, C      100-300          moderate          moderate       moderate          high         very low      very low
                Norpramin, Aventis; Others                                                                                                                                                             all TCAs cause
                                                                                                                                                                                                       slowed cardiac

                          Doxepin                                                                                                                                                                      conduction;
                                                    C, L      100-300          very high         very high      very high         high         very low        none                                    all TCAs may
                  Sinequan, Pfizer; Others                                                                                                                                                             lower seizure
                        Imipramine                  T, C,                                                                                                                                              some TCAs
                                                              100-300          very high           high         very high          high        very low        none
               Tofranil, Mallinckrodt; Others        IM                                                                                                                                                have
                       Nortriptyline                                                                                                                                      “therapeutic window”         therapeutic
                                                                                                                                                                          plasma level—must be         plasma levels
                  Pamelor, Mallinckrodt;            C, L      50-150           moderate          moderate       moderate          high         very low        none
                                                                                                                                                                          within 50-150 ng/mL
                  Aventyl, Eli Lilly; Others                                                                                                                              for efficacy
                       Protriptyline                  T        20-60           very high         very low       moderate          high         very low        high
                      Vivactil, Odyssey
                       Trimipramine                   C       100-300            high              high           high            high         very low        none
                     Surmontil, Odyssey

                                                    T, L       20-60             none               low           none          very high        high           low
                       Celexa, Forest                                                                                                                                     lower end of dosage range often
                                                                                                                                                                          effective for most depressed patients;
                        Fluoxetine                                                                                                                                        no need to titrate from smaller starting
                                                   C, T, L,
                                                               10-80             none              none           none          very high        high        very high    doses as done with TCAs; headache also
              Prozac/Sarafem, Eli Lilly; Others      ER
                                                                                                                                                                          common; much safer in overdose than
                                                                                                                                                                          TCAs; variable and significant inhibitory

                                                                                                                                                                          effect on hepatic P450 enzymes, except
                                                      T       100-300            none            moderate         none          very high        high           low
                   Luvox, Solvay; Others                                                                                                                                  citalopram; caution when coprescribed
                                                                                                                                                                          with drugs that undergo extensive
                        Paroxetine                                                                                                                                        hepatic metabolism and have a narrow
                                                    T, L       20-60              low               low           none          very high        high           low       therapeutic index; effective for panic
                   Paxil, GlaxoSmithKline                                                                                                                                 disorder, OCD, bulimia nervosa, social
                                                                                                                                                                          phobia, post-traumatic stress disorder,
                         Sertraline                                                                                                                                       and premenstrual dysphoria
                                                    T, L      50-200             none            very low         none          very high      very high     moderate
                        Zoloft, Pfizer

                                                      T        20-60           moderate             low         very high         high         very low      moderate
              Marplan, Oxford Pharm Services
                                                                                                                                                                          other uses: panic disorders, phobic

                        Phenelzine                                                                                                                                        disorders; Caution: high tyramine
                                                      T        45-90           moderate          moderate       very high         high         very low        none
                        Nardil, Pfizer                                                                                                                                    diet, sympathomimetic agents;
                                                                                                                                                                          divided dosing (bid-qid)
                                                      T        20-50           moderate            none         very high         high         very low      very high
                 Parnate, GlaxoSmithKline

                        Amoxapine                                                                                                                                         similar lethality in overdose to TCAs;
                                                      T       200-600             low               low            low            high         very low        none
                  Asendin, Lederle; Others                                                                                                                                EPS possible

                         Bupropion                                                                                                                                        safer in overdose than TCAs; SR
                Wellbutrin, GlaxoSmithKline           T       150-450            none              none           none            none        moderate         high       formulation offers bid (vs tid) dosing;
                                                                                                                                                                          avoid in patients with seizure disorders;
              Wellbutrin SR, GlaxoSmithKline         SR       150-400            none              none           none            none        moderate       moderate     Zyban used for smoking cessation

                        Maprotiline                                                                                                                                       similar lethality in overdose to TCAs; max-
                                                      T       150-225          moderate          moderate       moderate        moderate       very low        none       imum dosage limited due to seizure risk
                      Various generics

                        Mirtazapine                                                                                                                                       safer in overdose than TCAs; less sedation
                                                      T        15-45             none              high           none            none         very low        none
                    Remeron, Organon                                                                                                                                      at doses >15 mg/d; weight gain

                        Nefazodone                                                                                                                                        safer in overdose than TCAs; qhs or
                                                      T       300-600            none              high            low            none        moderate        very low
               Serzone, Bristol-Myers Squibb                                                                                                                              bid dosing; potent P450 3A4 inhibitor

                                                                                                                                                                          safer in overdose than TCAs; priapism rare
                         Trazodone                                                                                                                                        (1:1,000-1:10,000); not well tolerated at
                                                      T       200-600           very low         very high      very high         none        moderate         none
                Desyrel, Apothecon; Others                                                                                                                                antidepressant dosage; most commonly
                                                                                                                                                                          used as a hypnotic at 50-200 mg qhs

                                                                                                                                                                          SSRI-like; side effects most common; safer
                        Venlafaxine                                                                                                                                       in overdose than TCAs; qd for XR capsules,
                                                  C (XR), T   75-375             none               low          very low         high         very high     moderate
              Effexor/Effexor XR, Wyeth-Ayerst                                                                                                                            bid-tid dosing for tablets; also effective for
                                                                                                                                                                          generalized anxiety disorder

             * Few drug-to-drug comparison trials of sexual dysfunction frequency have been done; clomipramine and SSRIs are more likely than other antidepressants
               to cause delayed ejaculation and anorgasmia due to their serotoninergic effects.

14                 CNS NEWS SPECIAL EDITION • DECEMBER 2001
                    Mood Stabilizers*

                                                          Dosage                         Usual Adult                      Therapeutic
Class                              Agent                  Forms                          Daily Dosage                     Plasma Level                   Common Adverse Effects                                 Comments

                            Lithium Carbonate                                                                                                  nausea, fine hand tremor, increased            established standard treatment for bipolar
                                                                                     1,200-2,400 mg/d acute               0.8-1.2 mEq/L        urination and thirst; toxicity:                disorder; risk of hypothyroidism with
                       Eskalith CR, GlaxoSmithKline;        T, C, SR
                                                                                                                                               slurred speech, confusion, severe gastro-      maintenance therapy; avoid in pregnancy,
                          Lithobid, Solvay; Others                                 900-1,200 mg/d maintenance             0.6-1.2 mEq/L        intestinal effects, weight gain, acne          especially in first trimester

                              Carbamazepine                                                                                                                                                   hepatic enzyme inducer; alternative to
                                                            T, DR,                                                                             nausea, dizziness, sedation, headache,         lithium or valproic acid or adjunctive
                     Carbatrol, Shire US; Epitol, Teva;     ER, L
                                                                                         10-20 mg/kg/d                     6-12 mg/L†          dry mouth, constipation, rash                  treatment for bipolar disorder; avoid in
                        Tegretol, Novartis; Others                                                                                                                                            pregnancy, especially in first trimester

                                                                                                                                                                                              use of Depakote greatly minimizes gastro-
                               Valproic Acid                                                                                                                                                  intestinal effects; more effective than
                                                             T, C,                                                                             nausea, diarrhea, abdominal cramps,            lithium for rapid cycling and mixed bipolar
                       Depakene/Depakote, Abbott;                                        15-40 mg/kg/d                     50-120 mg/L
                                                            L, ER, I                                                                           sedation, tremor, weight gain, rash            disorder; loading dose 20 mg/kg; avoid
                                Others                                                                                                                                                        in pregnancy, especially in first trimester;
                                                                                                                                                                                              pancreatitis may occur in rare cases

                    * Alternative agents include gabapentin (Neurontin, Pfizer), lamotrigine (Lamictal, GlaxoSmithKline) and topiramate (Topamax, Ortho-McNeil), although very limited clinical data are available.
                    † Levels are not established for therapeutic efficacy, but rather are used to monitor for toxicity.

                                                                                              Approved          Approximate                                      Pharmacokinetic Parameters
                                                                                             Oral Adult          Equivalent
                                                                        Approved            Dosage Range            Doses         Dosage         Onset                       Metabolic           Active
Class                        Agent               Schedule              Indications             (mg/d)              (mg/d)         Forms          (PO)             t⁄
                                                                                                                                                                    2        Pathway            Metabolite                 Comments‡

                           Alprazolam                                                                                                                                                                              anterograde amnesia;
                                                                  anxiety disorders;             0.75-4                                                                                      alpha-hydroxy-
                                                    IV                                                              0.5               T           fast      intermediate      oxidation                            tid-qid dosing
                    Xanax, Pharmacia; Others                       panic disorder                1.5-10                                                                                      alprazolam

                       Chlordiazepoxide                            anxiety; alcohol                                                                                                                               variable
                                                                                                                                                                                             poxide, demoxepam,
                                                    IV               withdrawal;                  5-300             10             T, C, I        fast          long        N-dealkylation                        bioavailability
                       Librium, ICN; Others                                                                                                                                                  desmethyldiazepam,
                                                                preoperative sedation                                                                                                                             with IM dosing

                          Clonazepam                                                                                                                                                                               anterograde amnesia;
                                                                  seizure disorders;
                                                    IV                                             1-6             0.25               T        moderate         long          reduction             none           adjunctive for bipolar
                     Klonopin, Roche; Others                        panic disorder

                                                                                                                                                                                                                   disorder and psychoses

                          Clorazepate                              anxiety; seizure
                                                    IV            disorders; alcohol             7.5-60             7.5             T, C       very fast        long          oxidation
                    Tranxene, Abbott; Others                                                                                                                                                 pam, oxazepam

                                                               anxiety; alcohol with-
                            Diazepam                                                                                                                                                         desmethyldiazepam, variable
                                                               drawal; muscle spasm;
                                                    IV                                            2-20               5           T, SR, L, I   very fast        long          oxidation      3-hydroxydiazepam, bioavailability
                      Valium, Roche; Others                    preoperative sedation;
                                                                                                                                                                                             oxazepam           with IM dosing
                                                                  status epilepticus

                           Lorazepam                                                                                                                                                                               reliable
                                                                anxiety; preoperative
                      Ativan, Wyeth-Ayerst;         IV                                           0.5-10              1             T, L, I        fast          short        conjugation            none           bioavailability
                              Others                                                                                                                                                                               with IM dosing

                           Oxazepam                               anxiety disorders;
                                                    IV                                           30-120             15              T, C         slow           short        conjugation            none
                         Various generics                        alcohol withdrawal

                            Buspirone                                                                                                                                                                              no sedation, no
                                                                                                                                                                                                                   dependence; not useful
                      BuSpar, Bristol-Myers        No                    anxiety                  15-60              5                T        0.5-1.5 h        N/A              N/A                N/A
                                                                                                                                                                                                                   on prn basis; nausea,

                                                                                                                                                                                                                   dizziness, agitation

                          Hydroxyzine                             anxiety; pruritus;
                                                                  preoperative and                                                                                                                                 anticholinergic;
                      Vistaril/Atarax, Pfizer;     No                                            50-400             N/A           T, C, L, I      2h            N/A              N/A                N/A
                                                                    postoperative                                                                                                                                  sedation
                               Others                                 sedation

                    ‡ Avoid alcohol and other CNS depressants with these agents (except buspirone); drowsiness may impair ability to drive; use caution.

                                                                                                                                                                           CNS NEWS SPECIAL EDITION • DECEMBER 2001                      17
                                                                                                 Usual Daily Adult
                                                                                                  Dosage Range                                                  Pharmacokinetic Parameters
       Class                                              Agent                                       (mg/d)                  tpk (h)                 t ⁄ (h)
                                                                                                                                                        2            Metabolic Pathway                  Active Metabolites                             Comments§
                                                                                                       1-2                      2                     12-15                   oxidation                          none
                                                  ProSom, Abbott; Others

                                                        Flurazepam                                                                                                         oxidation                  hydroxyethylflurazepam            dosage accumulation; hangover

                                                                                                      15-30                     1                     40-150                                           flurazepam aldehyde              effect; little or no REM suppression;
                                                    Dalmane, ICN; Others                                                                                                 N-dealkylation                N-desalkylflurazepam             no REM rebound
                                                                                                      7.5-15                    2                         39                  oxidation                  2-oxoquazepam                  similar to flurazepam
                                                       Doral, Wallace

                                                        Temazepam                                                                                                                                                                       slow onset; little or no
                                                                                                      15-30                    2-3                    10-15                 conjugation                          none
                                                Restoril, Mallinckrodt; Others                                                                                                                                                          REM suppression

                                                         Triazolam                                                                                                                                                                      anterograde amnesia; rebound
                                                                                                    0.125-0.25               0.5-1.5                       2                  oxidation                          none
                                                 Halcion, Pharmacia; Others                                                                                                                                                             insomnia after discontinuation

                                                                                                                                        Onset (min)                         Duration (h)                         t 1⁄2 (h)

                                                                                                     25-100                                N/A                                   N/A                              3-10                  anticholinergic; OTC
                                                   Benadryl, Pfizer; Others

                                                                                                     25-100                                N/A                                   N/A                                10                  anticholinergic; OTC
                                                       Unisom, Pfizer

                                                                                                                                                                                                                                        very short duration of effect

                                                                                                       5-10                                30-60                                 1                                  1                   allows dosing during night up

                                                    Sonata, Wyeth-Ayerst                                                                                                                                                                to 4 hours before arising

                                                                                                       5-10                                30-60                                 2-4                                4
                                                     Ambien, Pharmacia

                                                      Chloral Hydrate                                                                                                                                                                   loses hypnotic efficacy within first
                                                                                                    500-2,000                               30                                   N/A                                8
                                                      Various generics                                                                                                                                                                  week; gastrointestinal irritation

                                               § Avoid alcohol and other CNS depressants with these agents; drowsiness may impair ability to drive; use caution.

                                                                                                                                                                Approved Adult             Relative Adverse-Effect Profiles
                                                                                                                            Dosage             Dosage            Oral Dosage Extrapyramidal                                 Orthostatic
                                                                                     Class                   Agent          Forms          Equivalents (mg)      Range (mg/d)  Side Effects Anticholinergic Sedation Hypotension                               Comments
                                                                                                      Chlorpromazine                                                                                                                                   allergic dermatitis;
                                                                                                                            T, SR, L, I,
                                                                                    Aliphatic         Thorazine, Glaxo-        SUPP                100||           50-2,000               moderate    moderate                 high        high        photosensitivity;
                                                                                                     SmithKline; Others                                                                                                                                ECG changes

                                                                                                                                                                                                                                                       patients on oral thio-
                                                                                                       Mesoridazine                                                                                                                                    ridazine who need
                                                                                                                              T, L, I                 50           100-400                  low         high                   high        high        injectable form may
                                                                                                      Serentil, Novartis                                                                                                                               receive mesoridazine
                                                                                                                                                                                                                                                       injection; ECG changes¶
                                                                                                                                                                                                                                                       irreversible retinal

                                                                                                       Thioridazine                                                                                                                                    pigmentation at doses
                                                                                                     Mellaril, Novartis;       T, L                100              50-800                  low         high                   high        high        >800 mg/d; decreased
                                                                                                          Others                                                                                                                                       libido; retrograde ejacu-
                                                                                                                                                                                                                                                       lation; ECG changes¶

                                                                                                       Fluphenazine                                                   2-40
                                                                                                    Prolixin, Apothecon;      T, L, I                 2                                   very high     low                    low         low
                                                                                                                                                                 12.5-75 mg IM
                                                                                                            Others                                               every 2 weeks
               Dopamine                                                                                                       T, L, I                 8              8-64                   high        low                    low         low
               receptor                                                            Piperazine        Trilafon, Schering;
               antagonists                                                                                  Others

                                                                                                      Stelazine, Glaxo-       T, L, I                 5              5-80                   high        low                    low         low
                                                                                                     SmithKline; Others

                                                                                                        Haloperidol                                                  2-40
                                                                               Butyrophenone       Haldol, Ortho-McNeil;      T, L, I                 2
                                                                                                                                                                 50-300 mg IM
                                                                                                                                                                                          very high   very low               very low    very low
                                                                                                           Others                                                every month
                                                                           Dibenzoxazepine           Loxitane, Watson;        C, L, I                 10            20-250                  high        low                  moderate   moderate

                                                                               Dihydroindolone                                 T, L                   10            50-225                  high        low                  very low      low         less or no weight gain
                                                                                                       Moban, Endo

                                                                                Thioxanthene                                   C, L                   4              5-60                   high        low                    low         low
                                                                                                   Navane, Pfizer, Others

18                                                 CNS NEWS SPECIAL EDITION • DECEMBER 2001
ANTIPSYCHOTICS                               (cont.)

                                                                                                          Approved Adult             Relative Adverse-Effect Profiles
                                                                              Dosage         Dosage        Oral Dosage Extrapyramidal                                 Orthostatic
                                    Class                 Agent               Forms      Equivalents (mg) Range (mg/d)   Side Effects Anticholinergic Sedation Hypotension                            Comments

                                                                                                                                                                                                WBC monitoring re-
                                                                                                                                                                                                quired due to risk of
                                                        Clozapine                                                                                                                               agranulocytosis; dose-
                            Dibenzodiazepine        Clozaril, Novartis;           T              50                75-900              rare         very high       very high        high       related seizure risk;
                                                         Others                                                                                                                                 hypersalivation and
                                                                                                                                                                                                significant weight gain;
                                                                                                                                                                                                no prolactin elevation

                                                                                                                                                                                                minimal weight gain;
                                                                                                                                                                                                transient and asympto-
                                                       Quetiapine                                                                                                                               matic increased liver
                           Dibenzothiazepine            Seroquel,                 T              N/A              300-800 #            rare         very low        moderate      moderate      function tests possible;
                                                       AstraZeneca                                                                                                                              must be given in divided
                                                                                                                                                                                                doses (bid); no prolactin
   Atypical                                                                                                                                                                                     elevation

   Dopamine and                                                                                                                                                                                 significant weight gain;
   serotonin recep-                                                                                                                                                                             transient and asympto-
   tor antagonists;                                                                                                                                                                             matic increased liver
   more effective                                      Olanzapine                                                                                                                               function tests possible;
                          Thienbenzodiazepine                                     T              N/A               10-20             very low         low           moderate         low
                                                                                                                                                                                                mild prolactin elevation;
   for negative                                   Zyprexa/Zydis, Eli Lilly
   symptoms of                                                                                                                                                                                  higher doses in smokers;
   schizophrenia                                                                                                                                                                                Zydis orally disintegrat-
   (amotivation,                                                                                                                                                                                ing formulation
   affect, isolation);
   significantly less
   EPS and lower                                                                                                                                                                                newest agent in class;
   risk for tardive                                                                                                                                                                             capsule should not be
   dyskinesia than                                                                                                                                                                              opened or crushed;
   with typical               Benzisothia-             Ziprasidone                                                                                                                              divided dosing (bid);
                                                                                                                                                                     low to        low to
   antipsychotics                                                                 C              N/A               40-160            very low       very low                                    least likely to cause
                             zolylpiperazine          Geodon, Pfizer                                                                                                moderate      moderate
                                                                                                                                                                                                weight gain; minimal
                                                                                                                                                                                                prolactin elevation;
                                                                                                                                                                                                caution in patients at
                                                                                                                                                                                                risk for QT prolongation

                                                                                                                                                                                                transient nausea,
                                                                                                                                                                                                insomnia possible; doses
                                                                                                                                                                                                above 6 mg/d associated
                                                       Risperidone                                                                                                                              with a higher incidence
                             Benzisoxazole                                       T, L            N/A                 2-6               low          very low           low        moderate      of EPS; less weight gain
                                                    Risperdal, Janssen                                                                                                                          than with clozapine or
                                                                                                                                                                                                olanzapine; greatest
                                                                                                                                                                                                prolactin elevation
                                                                                                                                                                                                among atypicals

                         || 100 mg chlorpromazine = 2 mg haloperidol
                         ¶ See prescribing information for blackbox warning on adverse events associated with ECG changes.
                         # 25-200 mg/d for elderly patients; 300-800 mg/d for adult patients with chronic schizophrenia.

Selected Readings
Allison DB, et al. Antipsychotic-induced weight gain: a comprehen-           Vancouver,Wash: Applied Therapeutics, Inc.; 1995:76-1–76-18.           cal efficacy and tolerability in the treatment of depression. CNS
sive research synthesis. Am J Psychiatry. 1999;156:1686-1696.                                                                                       Drugs. 1997;8:410-431.
                                                                             Dopheide JA, Stimmel GL,Yi DD. Focus on nefazodone: a serotoner-
American Psychiatric Association. Practice guidelines for major de-          gic drug for major depression. Hosp Formulary. 1995;30:205-212.        Pollack MH, Rosenbaum JF. Management of antidepressant-
pressive disorder in adults. Am J Psychiatry. 1993;4(suppl):1-26.                                                                                   induced side effects: a practical guide for the clinician. J Clin
                                                                             Grimsley SR. Anxiety disorders. In:Young LY, Koda-Kimble MA,
Bailey L,Ward M, Musa M. Clinical pharmacokinetics of benzodi-               eds. Applied Therapeutics: The Clinical Use of Drugs, 6th ed.          Psychiatry. 1987;48:3-8.
azepines. J Clin Pharmacol. 1994;34:804-811.                                 Vancouver,Wash: Applied Therapeutics, Inc.; 1995:76-1–76-31.           Preskorn SH. Recent pharmacologic advances in antidepressant
Baldessarini RJ. Current status of antidepressants: clinical pharma-         Grimsley SR, Jann MW. Paroxetine, sertraline, and fluvoxamine:         therapy for the elderly. Am J Med. 1993;94(suppl 5A):2S-12S.
cology and therapy. J Clin Psychiatry. 1989;50:117-126.                      new selective serotonin reuptake inhibitors. Clin Pharm. 1992;         Sheehan DV, Harnett-Sheehan K. The role of SSRIs in panic
Brown CS, Bryant SG. Monoamine oxidase inhibitors: safety and                11:930-957.                                                            disorder. J Clin Psychiatry. 1996;57(suppl 10):51-58.
efficacy issues. Drug Intell Clin Pharm. 1988;22:232-235.                    Jann MW. Clozapine. Pharmacotherapy. 1991;11:179-195.                  Stimmel GL. Mood disorders. In: Herfindal ET, Gourley DR, eds.
Calabrese JR, Fatemi SH, Kujawa M, et al. Predictors of response             Keck PE, McElroy SL, Tugrul KC, et al.Valproate oral loading in        Textbook of Therapeutics, 7th ed. Baltimore, Md: Williams &
to mood stabilizers. J Clin Psychopharmacol. 1996;16(suppl                   the treatment of acute mania. J Clin Psychiatry. 1993;54:305-308.      Wilkins Co; 2000:1203-1206.
1):24S-31S.                                                                                                                                         Stimmel GL. Psychotherapeutic agents. In: Knoben JE, Anderson
                                                                             Laird LK, Benefield WH. Mood disorders I: Major depressive disor-
Casey DE. Side effect profiles of new antipsychotic agents. J Clin           ders. In:Young LY, Koda-Kimble MA, eds. Applied Therapeutics:          PO, eds. Handbook of Clinical Drug Data, 9th ed. Stamford,
Psychiatry. 1996;57(suppl 11):40-45.                                         The Clinical Use of Drugs, 6th ed.Vancouver,Wash: Applied              Conn: Appleton & Lange; 1999:432-469.
Cates M,Wells BG, Thatcher W. Anxiety disorders. In: Herfindal ET,           Therapeutics, Inc.; 1995:76-1–76-28.                                   Stimmel GL. Schizophrenia. In: Herfindal ET, Gourley DR, eds.
Gourley DR, eds. Textbook of Therapeutics, 6th ed. Baltimore,                Love RC, Grothe DR. Mood disorders II: bipolar affective disor-        Textbook of Therapeutics, 7th ed. Baltimore, Md:Williams &
Md:Williams & Wilkins Co; 1996:1073-1093.                                    ders. In:Young LY, Koda-Kimble MA, eds. Applied Therapeutics:          Wilkins Co; 2000:1217-1228.
Chou JCY, Serper MR. Ziprasidone—a new highly atypical anti-                 The Clinical Use of Drugs, 6th ed.Vancouver,Wash: Applied              Stimmel GL, Dopheide JA, Stahl SM. Mirtazapine—an antidepres-
psychotic. Essent Psychopharmacol. 1998;2:463-485.                           Therapeutics, Inc; 1995:76-1–76-28.                                    sant with noradrenergic and specific serotonergic effects.
Cohen LJ. Risperidone. Pharmacotherapy. 1994;14:252-265.                     Marken PA, Stanislav SW. Schizophrenia. In:Young LY, Koda-Kimble       Pharmacotherapy. 1997;17:10-21.
                                                                             MA, eds. Applied Therapeutics: The Clinical Use of Drugs, 6th ed.      Sweet RA, Brown EJ, Heimberg RG, et al. Monoamine oxidase
Cooper BR,Wang CM, Cox RF, et al. Evidence that the acute behav-             Vancouver,Wash: Applied Therapeutics, Inc; 1995:75-1–75-26.
ioral and electrophysiological effects of bupropion (Wellbutrin) are                                                                                inhibitor dietary restrictions: what are we asking patients to give
mediated by a noradrenergic mechanism.                                       Morton WA, Sonne SC,Verga MA.Venlafaxine: a structurally               up? J Clin Psychiatry. 1995;56:196-201.
Neuropsychopharmacology. 1994;11:133-141.                                    unique and novel antidepressant. Ann Pharmacother.                     Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithi-
                                                                             1995;29:387-395.                                                       um. J Clin Pharmacol. 1994;34:280-285.
DeVane CL. Pharmacokinetics of the selective serotonin reuptake
inhibitors. J Clin Psychiatry. 1992;53(suppl 2):13-20.                       Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants and          Wincor MZ, Cyr M. Sleep disorders. In: Herfindal ET, Gouley DR,
                                                                             the cytochrome P450 system. Am J Psychiatry. 1996;153:311-320.         eds. Textbook of Therapeutics, 6th ed. Baltimore, Md:Williams
Dopheide JA. Sleep disorders. In:Young LY, Koda-Kimble MA, eds.
Applied Therapeutics: The Clinical Use of Drugs, 6th ed.                                        .
                                                                             Noble S, Benfield P Citalopram: a review of its pharmacology, clini-   & Wilkins Co; 1996:1133-1152.


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