Show Summary Details
Page of

(p. 441) Adult Psychopharmacology 

(p. 441) Adult Psychopharmacology
Chapter:
(p. 441) Adult Psychopharmacology
Author(s):

Christine Blasey

, Joseph K. Belanoff

, Charles DeBattista

, and Alan F. Schatzberg

DOI:
10.1093/med:psych/9780199845491.003.0090
Page of

Subscriber: null; date: 12 December 2018

General Guidance

Make the appropriate diagnosis but especially identify the target symptoms (see Table 90.1). Ideally, one would like to see the patient in a drug-free state for 1–2 weeks, although this is not always possible. Target symptoms are critical. Past history of medication response is quite predictive of current response. Family history of drug response is often helpful in making a medication choice.

Table 90.1. Adult Psychopharmacology

Indication

Class

Drug Name

Daily Dosage

Blood Level

Major depression

MAOI

Phenelzine (Nardil)

45–75 mg

MAOI

Tranylcypromine (Parnate)

30–50 mg

NRI

Buoropion (Wellbutrin)

300–450 mg (divided)

NRI

Bupropion (Alpenzin)

174–522 mg

SARI

Trazodone (Oleptro)

150–375 mg or XR 75–225 mg

SNRI

Venlafaxine (Effexor)

75–375 mg

SNRI

Duloxetine (Cymbalta)

20–60 mg

SNRI

Desvenlafaxine (Pristiq)

50–100 mg

SSRI

Fluoxetine (Prozac)

20–80 mg

SSRI

Sertraline (Zoloft)

50–200 mg

SSRI

Paroxetine (Paxil)

20–50 mg

SSRI

Fluvoxamine (Luvox)

50–300 mg

SSRI

Citalopram (Celexa)

20–40 mg

SSRI

Escitalopram (Lexapro)

10–20 mg

TCA

Imipramine (Tofranil)

150–300 mg

150–300 μ‎g/ml

TCA

Desipramine (Norpramin)

150–300 mg

150–300 μ‎g/ml

TCA

Amitriptyline (Elavil)

150–300 mg

100–250 μ‎g/ml

TCA

Nortriptyline (Pamelor)

50–150 mg

50–150 μ‎g/ml

Other

Mirtazapine (Remeron)

15–45 mg

Antidepressant augmentation

  • Lithium

  • Aripriprozole (Ability)

  • 600–1,800 mg

  • 2–20 mg

0.5–0.8 mEq/L

l-triodothyramine

25–50 mcg

Atypical depression

MAOI

Phenelzine (Nardil)

45–75 mg

Psychotic depression

  • ECT and Combination Therapy

  • (Antipsychotic/Antidepressant)

Dysthymia

SSRI

SSRI

Bipolar disorder

Lithium

900–2,000 mg

0.8–1.2 mEq/L*

Anticonvulsant

Carbamazepine (Tegretol)

400–1,600 mg

6–10 μ‎g/ml

Anticonvulsant

Divalproex sodium (Depakote)

750–2,250 mg (divided)

50–100 μ‎g/ml

SGA

Risperidone (Risperdal)

1–3 mg

SGA

Aripriprazole (Abilify)

2–30 mg

SGA

Lamotrigine (Lamictal)

25–400 mg

SGA

Asenapine (Saphris)

10–20 mg

SGA

Olanzapine (Zyprexa)

5–15 mg

SGA

Ziprasidone (Geodon)

80–160 mg

SGA

Quetiapine (Seroquel)

100–800 mg

SGA

Asenapine (Saphris)

20 mg

Schizophrenia

Low-potency antipsychotic

Chlorpromazine (Thorazine)

300–800 mg

High-potency antipsychotic

Haloperidol (Haldol)

3–10 mg

SGA

Risperidone (Risperdal)

1–8 mg

SGA

Clozapine (Clozaril)

300–900 mg

SGA

Olanzapine (Zyprexa)

5–20 mg

SGA

Quetiapine (Seroquel)

50–400 mg

SGA

Ziprasidone (Geodon)

40–160 mg

SGA

Aripiprazole (Abilify)

10–15 mg

SGA

Iloperidone (Fanapt)

12–24 mg

SGA

Asenapine (Saphris)

10–20 mg

SGA

Palperidone (Invega)

3–12 mg

SGA

Lurasidone (Latuda)

40–80 mg

Panic disorder

Benzodiazepine

Alprazolam (Xanax)

1–6 mg

Benzodiazepine

Clonazepam (Klonopin)

0.5–4 mg

SSRI

Fluoxetine (Prozac)

20–60 mg

SSRI

Sertraline (Zoloft)

50–200 mg

SSRI

Paroxetine (Paxil)

10–60 mg

SSRI

Venlafaxine (Effexor) XR

75–225 mg

Generalized anxiety disorder

SSRI

Paroxetine (Paxil)

12.5–37.5 mg

SSRI

Venlafaxine (Effexor) XR

75–225 mg

SSRI

Sertraline (Zoloft)

50–200 mg

Other

Buspirone (BuSpar)

15–30 mg (divided)

Obsessive-compulsive disorder

SSRI

Fluvoxamine (Luvox)

100–350 mg

SSRI

Fluoxetine (Prozac)

20–60 mg

SSRI

Paroxetine (Paxil)

20–60 mg

SSRI

Sertraline (Zoloft)

25–200 mg

TCA

Clomipramine (Anafranil)

150–250 mg

Social anxiety disorder

SNRI

Venlafaxine (Effexor) XR

75–225 mg

SSRI

Paroxetine (Paxil) CR

12.5–37.5 mg

SSRI

Sertraline (Zoloft)

25–200 mg

Body dysmorphic disorder

SSRI

SSRI

Insomnia

Antihistamine

Diphenhydramine

25–50 mg

GABA modulator

(Benadryl)

5–10 mg

GABA modulator

Zolpidem (Ambien)

5–20 mg

GABA modulator

Zaleplon (Sonata)

2–3 mg

Melatonin receptor agonist

  • Eszopiclone (Lunesta)

  • Ramelteon (Rozerem)

8 mg

SARI

Trazodone (Oleptro)

50–100 mg

Narcolepsy

Psychostimulant

Modafanil (Provigil)

200 mg

GHB (Xyrem)

6–9 g

Dextroamphetamine (Dexedrine)

10–40 mg

TCA

Protriptyline (Vivactil)

10–40 mg

Schizotypal personality disorder

Antipsychotic

Haloperidol (Haldol)

3 mg

Borderline personality disorder

Antipsychotic

Loxapine (Loxitane)

5–25 mg

Anticonvulsant

Valproic Acid (Depakote)

750 mg

SSRI

Fluoxetine (Prozac)

20–60 mg

Avoidant personality disorder

MAOI

Phenelzine (Nardil)

45–60 mg

SSRI

Fluoxetine (Prozac)

10–40 mg

Alcohol withdrawal

Benzodiazepine

Chlordiazepoxide (Librium)

25–100 mg Q 6 h

Benzodiazepine

Lorazepam (Ativan)

1 mg Q 1 hr PRN pulse > 110, BP > 150/100

Vitamin

Thiamine

100 mg 1–3×QD

Vitamin

Folic acid

1 mg QD

Vitamin

Multivitamin

1 tablet QD

Heroin withdrawal

  • Opioid

  • Opioid agonist/antagonist

  • Methadone

  • Buprenorphine and

  • Natoxone (Suboxone)

  • 5 mg Q 4 h as needed on first day then decrease by 5 mg QD until 0

  • 16/4 mg

Relapse prevention

Disulfiram (Antabuse)

500 mg QD for 2 weeks then 250 Q D (1st dose at least 12 h after last ETOH use)

Opioid agonist

Naltrexone (ReVia)

25 mg QD for 1–2 days then 50 mg (1st dose at least 7–10 days after last opioid use)

Bulimia nervosa

SSRI

Fluoxetine (Prozac)

40–60 mg

Alzheimer’s dementia

Anticholinesterase

Tacrine (Cognex)

Start at 40 mg and raise by 40 mg every 6 weeks up to 110 mg

Anticholinesterase

Donezepil (Aricept)

5 mg

Anticholinesterase

Galantamine (Razadyne)

4–24 mg

Anticholinesterase

Rivagistigmine (Exelon)

3–12 mg

NMDA receptor antagonist

Memantine (Namenda)

5–20 mg

* Levels ≥1.5 mEq/L may be toxic, and levels ≥ 2.5 mEq/L may be fatal.

MAOI, monoamine oxidase inhibitors; NRI, norepinephrine reuptake inhibitor; SARI, serotonin antagonist and reuptake inhibitor; SGA, second-generation antipsychotic; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

Major Depression

Major depression is a common and debilitating illness (lifetime prevalence of approximately 16%). Success rates for psychopharmacological interventions are approximately 60%–70%.

  • Bupropion. Bupropion is a norepinephrine and dopamine reuptake inhibitor. Since introduced in the United States in 1989, it has proved to be an effective, safe (and underutilized) antidepressant. Response and remission rates are comparable to the selective serotonin reuptake inhibitors. Initially, the introduction of buproprion had been delayed after the occurrence of seizures in patients with bulimia.

  • Mirtazapine. Mirtazapine enhances both noradrenergic and serotonergic transmission. Side effects include weight gain and sedation but few sexual side effects.

  • Monoamine oxidase inhibitors (MAOIs). MAOIs are probably underutilized because of concern about tyramine-induced hypertensive crisis (extreme high blood pressure brought on by eating certain foods, including aged cheese, aged meat, and red wine, while using an MAOI).

  • Selective serotonin reuptake inhibitors (SSRIs). The release of fluoxetine in 1988 greatly expanded the number of patients with major depression treated pharmacologically. The SSRIs are virtually never lethal in overdose, and their side-effect profiles are relatively benign.

  • Trazodone. Trazodone is an inhibitor of serotonin reuptake, an agonist at some serotonin receptors, and an antagonist at others. It is also an alpha-adrenergic blocker and an antihistamine, so common side effects include orthostatic hypotension and sedation. Although the primary indication for trazodone is major depression, it is quite effective in low doses (50–100 mg) as a hypnotic.

  • Tricyclic antidepressants (TCAs). TCAs have demonstrated proven efficacy in major depression but can produce side effects, ranging from the annoying (dry mouth) to the dangerous (arrhythmia). Desipramine and nortriptyline are least likely to produce (p. 442) (p. 443) (p. 444) sedation, postural hypotension, and anticholinergic side effects.

  • Venlaflaxine and duloxetine. Venlafaxine is a nonspecific reuptake inhibitor. Unlike the TCAs, venlafaxine does not block cholinergic, histaminergic, or adrenergic receptors, so its side-effect profile is relatively benign. Duloxetine is an effective, approved treatment of major depression, generalized anxiety disorder, and fibromyalgia.

  • Electroconvulsive therapy (ECT). When depression is accompanied by delusions or is very severe, ECT is the treatment of choice.

  • Adjunct therapy. If a patient’s depression has been nonresponsive to a 6-week course of antidepressants at appropriate dosages, adjunct therapy with either lithium or thyroid hormone is an alternative.

  • Atypical depression (hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity, mood reactivity). MAOIs have demonstrated superior efficacy compared with TCAs in treating this variation of major depression.

  • Psychotic (delusional) depression. Antidepressant medication alone is usually ineffective. The combination of an antidepressant and an antipsychotic is effective in some patients. ECT is probably the most effective treatment.

  • Dysthymia. For many years the prognosis for individuals with dysthymia was poor. There is now increasing evidence that long-term use of antidepressants, particularly SSRIs, is quite effective in improving dysthymia and perhaps in preventing declines into major depression.

Bipolar Disorder

The most effective acute treatment for manic psychotic agitation (virtually always administered in the emergency room) is an antipsychotic medication (e.g., haloperidol) combined with a benzodiazepine (e.g., lorazepam). Shortly thereafter, sometimes following a negative toxicology screen, a mood-stabilizing agent must be started.

  • Lithium. Lithium remains the gold standard for the treatment of bipolar disorder. Seventy to eighty percent of acutely manic patients respond to lithium, but it often takes 1–3 weeks for a full response.

  • Carbamazepine. Primarily used as an anticonvulsant, carbamazepine also has been shown to be quite effective in treating bipolar disorder.

  • Valproic acid. Valproate (primarily used now in divalproex sodium form) has been granted FDA approval for the treatment of bipolar disorder. It appears that valproate may be especially effective in the treatment of rapid-cycling bipolar disorder and mixed (p. 445) manic-depressive states. Because there are many drug–drug interactions with valproic acid, the prescribing physician must be made aware of all medication changes (including over-the-counter drugs).

  • Other anticonvulsants. Lamotrigine is currently being studied for the treatment of bipolar disorder. Other anticonvulsants used for bipolar disorder include tiagabine, oxcarbazepine, gabapentin, and levetiracetam, although none of these are currently approved by the FDA for use in bipolar disorder.

  • Second-generation antipsychotic medications. These medications have been commonly used to treat schizophrenia. Their mechanism of action is described in the subsequent section on schizophrenia treatment. More recently, these types of antipsychotic medications are being prescribed for the treatment of bipolar disorder. In 2006, quetiapine became the first atypical antipsychotic to also receive FDA approval for the treatment of bipolar depressive episodes. Quetiapine also relieves the symptoms of severe manic episodes. Risperidone and ziprasidone are other second-generation antipsychotics that may be prescribed for controlling manic or mixed episodes. In 2009, the FDA approved asenapine for schizophrenia and bipolar disorder in adults. Other commonly used second-generation antipsychotics include olanzapine and aripiprazole. Olanzapine, when given with an antidepressant medication, may help relieve symptoms of severe mania or psychosis. Olanzapine is also available in an injectable form, which quickly treats agitation associated with a manic or mixed episode. Olanzapine can be used for maintenance treatment of bipolar disorder as well. However, studies show that people taking olanzapine typically gain significant weight and may experience other metabolic side effects that can increase their risk for diabetes and heart disease. Aripiprazole is approved for treatment of a manic or mixed episode. Aripiprazole is also used for maintenance treatment after of bipolar disorder. As with olanzapine, aripiprazole also can be injected for urgent treatment of symptoms of manic or mixed episodes of bipolar disorder.

Schizophrenia

Antipsychotic medication is often divided into two groups, first generation and second generation. Both groups are effective in treating the symptoms of schizophrenia, but they differ in terms of their side-effect profile. All first-generation antipsychotics are dopamine-2 receptor blockers. Second-generation antipsychotics are less prominent dopamine-2 receptor blockers, and they tend to block many other receptors, particularly serotonin-2 receptors.

First-Generation Antipsychotics: Dopamine Receptor Antagonists (D2 Receptors)

All traditional antipsychotic medications work essentially the same way and have the same side-effect profile. Medications such as chlorpromazine with a relatively low affinity for D2 receptors (“low potency”) require a higher dose, and medications with a relatively high affinity for D2 receptors such as haloperidol (“high potency”) require a lower dose. The dopamine receptor antagonists are effective in the short and long term; they reduce current symptoms (e.g., hallucinations, delusions, and agitation) and can prevent future relapses. These medications have adverse effects, including sedation, tardive dyskinesia, and severe agitation. The low-potency medicines may also have cardiac and orthostatic hypotensive side effects and may lower the seizure threshold.

Second-Generation Antipsychotics: Dopamine/Serotonin Receptor Antagonists

Aripiprazole, asenapine, clozapine, iloperidone, olanzapine, risperidone, quetiapine, and ziprasidone are all less likely than the first-generation antipsychotics to cause motoric side effects. However, the second-generation antipsychotics are associated with weight gain and metabolic problems. The second-generation antipsychotics may be more effective than the (p. 446) first generation in treating the negative symptoms (e.g., emotional withdrawal) and cognitive deficits of schizophrenia.

Anxiety Disorders

Biological theories of anxiety disorders have pointed to problems in the norepinephrine, serotonin, and gamma-aminobutyric acid neurotransmitter systems. As a consequence, a wide variety of medications has been tried with varying success.

  • Panic disorder. Antidepressants should be considered the first line of pharmacotherapy for patients with panic disorder. Benzodiazepines have also been shown to be effective in treating panic disorder but have a number of disadvantages over antidepressants. They often produce sedation, increase the effects of alcohol, produce dys-coordination, and are associated with dependence and withdrawal. Patients can have severe panic attacks while withdrawing from benzodiazapines. Response rates to the antidepressants paroxetine and sertraline are superior to benzodiazepines, although they work less rapidly.

  • Generalized anxiety disorder (GAD). The SNRI venlafaxine is an effective approved treatment for GAD. Other antidepressants have also been shown to be effective. Benzodiazepines have been frequently used to treat patients with GAD. They are effective in the short run for symptom relief. However, for all of the reasons listed earlier, their longer term use is problematic. Buspirone, a serotonin partial agonist, has been shown to be as effective as benzodiazepines in patients with GAD.

  • Social anxiety disorder. The SNRI venlafaxine is an effective approved treatment for social anxiety disorder. Antidepressants are effective for reducing symptoms and disability from social anxiety disorder. The SSRIs paroxetine and sertraline are approved, effective treatments for social anxiety disorder. Alprazolam and phenelzine have been reported to produce improvement in symptoms of social anxiety disorder. Beta-blockers have helped reduce physical manifestations of performance anxiety (in events like public speaking) but are not particularly effective with social anxiety.

  • Obsessive-compulsive disorder (OCD). OCD is both relatively common and quite responsive to pharmacotherapy. All of the SSRIs have been shown to be effective in reducing the symptoms of OCD. Fluvoxamine, clomipramine, fluoxetine, paroxetine, and sertraline are FDA-approved treatments of OCD. Clomipramine, a nonspecific (but very serotonergically potent) reuptake inhibitor, has been best studied and is often effective.

Sleep Disorders

  • Insomnia. Insomnia is a common symptom in many psychiatric illnesses, particularly major depression. Insomnia often resolves as the depressive episode resolves. However, when insomnia is particularly distressing to the patient, low doses of trazodone or diphenhydramine are often effective in improving sleep. Patients suffering from insomnia can benefit from hypnotic effects of benzodiazepines or from nonbenzodiazepine agonists, which include zolpidem, zaleplon, and triazolam. The benzodiazepine agonists are less likely to cause rebound insomnia or tolerance. Because insomnia may be a symptom of a physical or psychiatric disorder, hypnotics should not be used for more than 7 to 10 days without a thorough evaluation as to the cause of the insomnia.

  • Narcolepsy. Psychostimulants (i.e., amphetamines) have long been accepted as valuable treatment for the daytime sleepiness seen in narcolepsy. Stimulants do not prevent the cataplexy that some narcoleptic patients experience, but either TCAs or SSRIs in combination with stimulants may be helpful. Modafinil has proven efficacy in maintaining wakefulness in patients with narcolepsy. In 2002, the FDA approved gamma-hydroxybutyric acid (p. 447) (GHB) for the treatment of narcolepsy with cataplexy.

Personality Disorders

Despite the fact that pharmacotherapy has increasingly gained acceptance as a treatment option for severe personality disorders, there are few well-controlled studies that document pharmacological efficacy. In addition, many specific personality disorders have not been studied pharmacologically at all. Those that have include the following:

  • Schizotypal personality disorder. It appears that schizotypal personality disorder has a genetic association with schizophrenia, so it is not surprising that there is some evidence for improvement with low-dose antipsychotic medication.

  • Borderline personality disorder (BPD). SSRIs seem to help in BPD, particularly with impulsive aggression and affective instability. Low-dose antipsychotic medication is often effective in improving hostility and cognitive perceptual disturbances. Anticonvulsants, particularly valproic acid, seem to improve behavioral dyscontrol; benzodiazepines and noradrenergic antidepressants often seem to make behavioral dyscontrol worse.

  • Avoidant personality disorder. There are no double-blind placebo-controlled studies, but there is evidence that MAOIs, SSRIs, beta-adrenergic receptor antagonists, and benzodiazepines may be useful in combination with psychotherapy.

Psychoactive Substance Abuse and Withdrawal

  • Intoxication. Most treatment for serious intoxication is focused on physiological support (controlling blood pressure, heart rate, respiration, etc.). The psychosis seen in amphetamine and cocaine intoxication may be treated with standard antipsychotics, often in combination with benzodiazepines (which help with agitation).

  • Withdrawal. Withdrawal from alcohol, benzodiazepines, and barbiturates is similar and is potentially life-threatening. All of these withdrawals are best pharmacologically treated with benzodiazepines. Lorazepam (Ativan) is recommended for patients with significant liver disease because its metabolism is less impaired in advanced liver disease. Methadone and clonidine are used in opiate withdrawal.

  • Relapse prevention. The prevalence of substance abuse disorders, particularly alcohol abuse and dependence, has sparked interest in pharmacological methods to help prevent relapse. Disulfiram (Antabuse) has been tried for many years, although its popularity has certainly declined. Naltrexone, a synthetic opioid antagonist, is used in the treatment of alcoholism and narcotic dependence. Naltrexone aids abstinence by blocking the “high” caused by narcotics. Suboxone (Buprenorphine) is effectively used for opioid withdrawal and relapse prevention.

Somatoform Disorders

Most of the somatoform disorders are ineffectively treated with current medication, and, unfortunately, psychoactive medication therapies are probably overused significantly. The one exception is body dysmorphic disorder, where the effective use of serotonergic agents (particularly SSRIs) has dramatically improved the prognosis for affected patients.

Eating Disorders

  • Anorexia nervosa. Unfortunately, there is no shining star of pharmacological treatment for this life-threatening illness. Antipsychotic medication has not worked, and cyproheptadine, amitriptyline, and fluoxetine have had limited success. (p. 448)

  • Bulimia nervosa. Antidepressants work very well in the treatment of bulimia apart from their ability to elevate mood.

Impulse-Control Disorders

Among the impulse-control disorders, intermittent explosive disorder and trichotillomania are most often treated pharmacologically.

  • Intermittent explosive disorder. Anticonvulsants are used most often, although the results are mixed. Benzodiazepines often make matters worse, with more behavioral dyscontrol. There is increasing case evidence that buspirone (often in higher doses than used in generalized anxiety disorder) may be effective.

  • Trichotillomania. New pharmacological studies are taking place with both serotonergic antidepressants and the anticonvulsant valproic acid.

References, Readings, and Internet Sites

Fournier, J. C., DeRubeis, R. J., Hollon, S. D. Dimidjian, S., Jay, D.,. Amsterdam, J. D., … Fawcett, J. (2010). Antidepressant drug effects and depression severity. Journal of the American Medical Association, 303(1), 47–53.Find this resource:

Kane, J. M., & Correll, C. U. (2010). Pharmacologic treatment of schizophrenia. Dialogues in Clinical Neuroscience, 12(3), 345–357.Find this resource:

Katzman, M. A. (2009). Current considerations in the treatment of generalized anxiety disorder. CNS Drugs, 23(2), 103–120.Find this resource:

Koran, L. M., Hanna, G. L., Hollander, E., Nestadt, G., Simpson, H. B., & American Psychiatric Association. (2007). Practice guideline for the treatment of patients with obsessive–compulsive disorder. American Journal of Psychiatry, 164(7 Suppl), 5–53.Find this resource:

PDR Network. (2012). Physician’s desk reference. Montvale, MJ: Author.Find this resource:

    Rush, J., Trivedi, M. H., Wisniewski, S. R., Stewart, J. W., Nierenberg, A. A., Thase, M. E., … Fava, M. (2006). Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. New England Journal of Medicine, 354(12), 1231–1242.Find this resource:

    Sadock, B., Sadock, V., & Sussman, N. (2006). Pocket handbook of psychiatric drug treatment (4th ed.). Philadelphia, PA: Lippincott Williams & Wilkins.Find this resource:

      Schatzberg, A. F., Cole, J., & DeBattista, C. (2010). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.Find this resource:

        US Food and Drug Administration. (2012). Drug interactions: What you should know. Retrieved January 2013, www.fda.gov/Drugs/ResourcesForYou/ucm163354.htm

        Related Topics

        Chapter 91, “Understanding Side Effects and Warnings in Psychopharmacology”

        Chapter 92, “Pediatric Psychopharmacology”

        Chapter 94, “Herbal Treatments for Psychological Disorders”