Psychiatric Disorders

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CHAPTER 19 Psychiatric Disorders

I. Introduction

A. Psychiatric disorders

1. Patients who have one psychiatric disorder will usually have multiple psychiatric disorders.
2. Patients must be carefully assessed to develop an individualized treatment plan.
3. Must determine if new symptoms are due to treatment or new psychiatric disorder.

B. Therapeutic options

1. Psychotherapy

a. Combination of psychotherapy and pharmacotherapy is the optimal approach for most patients
b. Psychotherapy is often difficult to obtain or is not covered by insurance.
c. Helps with psychosocial or coping skills that may contribute to the specific illness

2. Pharmacotherapy

a. Improves mood and somatic symptoms

3. Other modalities

a. Electroconvulsive therapy (ECT)

(1) Very effective form of treatment, unknown mechanism of action, generally reserved for treatment-resistant or delusional depression.
(2) Controversial form of treatment
(3) Patients who have responded to it in the past and have relapsed may benefit.
(4) Most common side effects include short-term memory problems, which tend to improve with time after treatment.

II. Anxiety disorders

A. Types

1. Generalized anxiety disorder (GAD): 6 months or more of excessive worry or anxiety generally with an unidentified cause
2. Panic disorder: discrete periods of sudden intense fear or terror and feelings of impending doom. Usually the precipitating cause is not known; the patient can become conditioned to believe it is caused by some environmental cause. Disorder can lead to agoraphobia: fear or avoidance of certain situations (e.g., going to the store) because they think they will have an attack.
3. Obsessive-compulsive disorder (OCD): characterized by obsessive or intrusive thoughts that one cannot control and that are repetitive in nature: ritualistic behaviors (e.g., repetitive hand washing, combing the hair, cleaning the house)
4. Posttraumatic stress disorder (PTSD): follows a traumatic event and is characterized by increased arousal and avoidance of stimuli that approximate the original traumatic event
5. Phobic disorders: characterized by anxiety out of proportion to the stimulus that is the object of fear

B. Treatments

1. Benzodiazepines (Table 19-1)

a. Anxiolytic treatment and prophylaxis of panic attacks
b. A reduction in anxiety may be seen with first dose.
c. Five properties common to all

(1) Anxiolytic
(2) Hypnotic
(3) Muscle relaxant
(4) Anticonvulsant
(5) Amnesic

d. Tolerance to the anxiolytic action is uncommon, but tolerance may occur to the hypnotic action (which is why benzodiazepines should only be used for insomnia for a few days at a time).
e. Anxiolytics are differentiated by half-life, metabolites (active/inactive), potency.
f. Abrupt cessation can lead to withdrawal, depending on length of therapy.
2. Antidepressants (discussed in more detail under Depression)

a. Tricyclic antidepressants (TCA)

(1) Anxiety treatment and prophylaxis of panic disorders

b. Selective serotonin reuptake inhibitors (SSRI)

(1) Anxiety treatment and prophylaxis of panic disorders

c. Serotonin-norepinephrine reuptake inhibitors

(1) Venlafaxine (Effexor) has FDA approval for treatment of generalized anxiety disorder.

d. Buspirone

(1) May be effective for anxiety
(2) Little value for panic disorder
(3) Long onset of action: 4–6 weeks, must use another anxiolytic until onset occurs

e. Beta blockers

(1) May block peripheral symptoms of panic disorders

f. Monoamine oxidase inhibitors (MAOIs)

(1) May be effective for panic disorders in patients with atypical depression

III. Schizophrenia

Table 19-1 Benzodiazepines used for Anxiety

Agent Half-life (hours) Equivalent Dose (mg, approximate only)
Alprazolam (Xanax) 6–12 1
Chlordiazepoxide (Librium) 5–30 25
Diazepam (Valium) 20–100 10
Lorazepam (Ativan) 10–18 1
Oxazepam (Serax) 4–15 10

Psychotic disorder that has multiple symptoms involving perception (e.g., hallucinations), ideation, reality (e.g., delusions), cognition (e.g., loose associations), emotions (e.g., flat affect), behavior (e.g., disorganization), attention, concentration, motivation (e.g., avolition or lack of motivation), concentration, judgment.

Schizophrenia usually occurs between adolescence and early adulthood, earlier in men (early 20s) than women (late 20s to early 30s). The incidence is almost equal between sexes.

A. Signs and symptoms

1. Positive

a. Delusions

(1) Erroneous beliefs that involve misinterpretations of reality and are relatively resistant to evidence that refutes them
(2) A “fixed” delusion that will not change no matter how much evidence is offered to the contrary

b. Hallucinations

(1) Perceptual abnormalities that can involve any sensory system
(2) Schizophrenia often involves auditory hallucinations that can be persecutory (e.g., someone’s going to get me), paranoid (e.g., someone is watching me), commanding (e.g., someone told me to do it), etc.

2. Negative

a. Lack of facial expression
b. Blank stares
c. Monotone and monosyllabic speech
d. Seeming lack of interest in the world and other people
e. Inability to feel pleasure or act spontaneously
f. Disorganization (speech, behavior, poor attention)

3. Cognitive

a. Difficulty paying attention
b. Memory problems
c. Difficulty planning or structuring activities
d. Lack of insight and understanding

B. Four phases

1. Prodromal

a. Characterized by gradual development of symptoms that may go unnoticed until major symptom occurs
b. May include isolation, deterioration of hygiene, loss of interest in work, or school, dysphoria

2. Acute phase

a. Full-blown episode of psychotic behavior
b. Patient may be unable to care for self at times

3. Stabilization phase

a. Acute symptoms begin to decrease
b. Phase may last for several months

4. Stable phase

a. Acute symptoms have markedly declined and may not be present
b. Nonpsychotic symptoms such as anxiety and depression may be present (complete remission without symptoms is uncommon)

C. Risk factors for schizophrenia

1. Family history of schizophrenia
2. Lower socioeconomic status
3. Poor birth history
4. Intrauterine trauma
5. Living in an urban area
6. Stress
7. Being born during the winter

D. Treatment

1. Antipsychotic agents

a. Two classes: atypical (or second generation) and conventional antipsychotics
b. Atypical antipsychotics (Table 19-2)

(1) Block dopamine, serotonin, and other neurotransmitters

(a) Block dopamine more selectively than conventional antipsychotics, thereby reducing the probability of extrapyramidal symptoms (EPS)

(2) First-line therapy
(3) Maintain indefinitely
(4) Complications of treatment

(a) Metabolic syndrome (excess abdominal fat, insulin resistance, hyperlipidemia, hypertension)
(b) Tardive dyskinesia is possible with all atypical antipsychotic agents.

c. Conventional antipsychotic agents

(1) Primarily block dopamine
(2) Classified as high, mild, or low potency depending on affinity for dopamine
(3) High potency

(a) Haloperidol (Haldol)

(i) Prototypical high-potency drug
(ii) Haloperidol decanoate available as IM depot

(b) Fluphenazine (Prolixin)

(i) IM depot form also available

(c) Thiothixene (Navane)

(i) Notably high incidence of akathisia (“inner restlessness”)

(d) Trifluoperazine (Stelazine)
(e) Pimozide (Orap)

(i) Approved only for Tourette syndrome

(4) Mild potency

(a) Perphenazine (Trilafon)
(b) Molindone (Moban)

(i) May cause weight reduction

(c) Loxapine (Loxitane)

(i) High affinity for dopamine and serotonin receptors

(d) Prochlorperazine (Compazine)

(5) Low-potency

(a) Chlorpromazine (Thorazine)

(i) Prototypical low-potency drug

(b) Thioridazine (Mellaril)

(i) May cause QT prolongation

(c) Mesoridazine (Serentil)

(6) Complications of treatment: associated with EPS and increased prolactin (hyperprolactinemia)

IV. Mood disorders

A. Depression

1. Major depressive disorder

a. Unipolar depression, may experience one (first episode is a “major depressive disorder single episode”) or more episodes (“major depressive disorder recurrent”)
b. Number of episodes and periods between them is variable from patient to patient.
c. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)

(1) Depressive syndromes are defined in the DSM-IV.
(2) Health professionals use the DSM-IV criteria to diagnose depressive disorders and other mental disorders.

2. Dysthymia

a. Chronic condition of depressed mood for at least 2 years
b. Symptoms not severe enough to meet DSM-IV criteria for major depressive disorder
c. Periods of normal mood last only for short periods
d. Patients may also experience major depressive disorder (“double depression”).
e. May be difficult to treat, often not as responsive to therapy as major depressive disorder

3. Treatment

a. FDA warning: Patients taking antidepressants should be monitored closely for signs of suicide, worsening depression, anxiety, and panic attacks.

4. Tricyclic antidepressants (TCA)

a. Mechanism of action

(1) Block reuptake of norepinephrine
(2) Less effect on serotonin
(3) Increases concentration of norepinephrine in synapse

b. Dose

(1) Start with low dose and titrate up

c. Adverse effects

(1) Anticholinergic side effects
(2) Drowsiness
(3) Insomnia/agitation
(4) Gastrointestinal (GI) distress
(5) Weight gain
(6) Orthostatic hypertension
(7) Cardiac arrhythmia

d. Drug interactions

(1) TCA are metabolized by CYP enzymes, and drugs that inhibit/induce CYP may alter the concentrations of TCA.

e. Cautions

(1) Avoid during pregnancy
(2) Drugs that prolong the QT interval should be avoided with TCA.

f. Examples

(1) Imipramine, amitriptyline, amoxapine, desipramine, doxepin, nortriptyline, protriptyline, trimipramine

5. Serotonin reuptake inhibitors (SSRI)

a. Considered first-line therapy
b. May also be useful for OCD, bulimia nervosa, panic disorder, and premenstrual syndrome (PMS)
c. Mechanism of action

(1) Downregulates postsynaptic serotonin receptor in response to the increased amount of synaptic serotonin

d. Adverse effects

(1) Generally mild
(2) May be associated with sexual dysfunction
(3) Serotonin syndrome caused by overstimulation of serotonin receptors

e. Examples

(1) Fluoxetine (Prozac)

(a) Elimination half-life of 4–6 days
(b) Potent inhibitor of CYP 2D6; mild inhibitor of CYP 3A4
(c) Usual adult initial dose: 20 mg daily; may be increased to 80 mg/day if needed (immediate-release)

(2) Paroxetine (Paxil)

(a) Potent inhibitor of CYP2D6
(b) Possibility of birth defects if taken during first trimester of pregnancy
(c) Usual adult initial dose: 20 mg daily; may be increased to 40 mg daily (immediate-release)

(3) Sertraline (Zoloft)

(a) Has the most dopaminergic reuptake blockage than any other SSRI
(b) Mild inhibitor of CYP 2D6
(c) Usual adult initial dose: initial 50 mg daily; maintenance 50–100 mg daily. Doses of a maximum of 200 mg daily may be used.
(d) Side effects: gastrointestinal complaints (nausea, diarrhea)

(4) Citalopram (Celexa)

(a) Major CYP 2C19 and 3A4 substrate
(b) Usual Adult initial dose: Dose 20–40 mg daily

(5) Escitalopram (Lexapro)

(a) Because escitalopram is the enantiomer of citalopram, it is considered to be more potent than citalopram.
(b) Major substrate of CYP C19, 3A4, and weak inhibitor of 2D6
(c) Usual adult initial dose: 10 mg daily (immediate-release)

(6) Fluvoxamine (Luvox)

(a) Approved for obsessive compulsive disorder
(b) Potent inhibitor of CYP450, 1A2, 3A4, and 2C19
(c) Usual Adult initial dose: Dose 50 mg daily; may increase to 150–250 mg daily

6. Monoamine oxidase inhibitors (MAOI)

a. Monoamine oxidase breaks down norepinephrine, epinephrine, dopamine, and serotonin; interference causes neurotransmitters to accumulate in the synapse
b. May increase tyramine and cause hypertensive crisis (headache, stiff neck, palpitations, chest pain, increased or decreased heart rate, nausea/vomiting, pyrexia, chills, flushing), cerebrovascular accident, death
c. Tyramine is broken down by MAO-A, and inhibiting its action may result in excessive build-up of tyramine. Patients taking MAOI should limit intake of foods that contain tyramine, including aged cheese, wines like Chianti, broad bean (fava bean) pods, chocolate, soy sauce, and others.
d. Drug interactions

(1) Avoid sympathomimetics (e.g., pseudoephedrine), reserpine, TCA, levodopa, and anticholinergic agents

e. Examples of MAOI

(1) Tranylcypromine, phenelzine, isocarboxazid, moclobemide, selegiline

7. Atypical antidepressants

a. Bupropion (Wellbutrin)

(1) Useful if patient did not respond to TCA or SSRI
(2) Also used for smoking cessation (Zyban)
(3) Mechanism of action: blocks reuptake of norepinephrine
(4) Usual adult dose: 150 mg twice daily
(5) Adverse effects: increased risk of seizures
(6) Drug interactions: Use cautiously in patients using other agents that may lower the seizure threshold (e.g., antipsychotics, antidepressants, fluoroquinolones)

b. Nefazodone (Serzone)

(1) Mechanism of action

(a) Inhibits reuptake of serotonin and norepinephrine
(b) Also blocks alpha-1 receptors

(2) Usual adult dose: 300–600 mg/day in two divided doses
(3) Adverse effects: associated with hepatic injury
(4) Drug interactions

(a) Major CYP 2D6 substrate
(b) Major CYP 3A4 inhibitor

c. Trazodone (Desyrel)

(1) Mechanism of action

(a) Serotonin antagonist
(b) Also blocks histamine and alpha-1 receptors

(2) Dose

(a) Usual adult dose: 150 mg daily in three divided doses
(b) Maximum 600 mg daily

(3) Adverse effects

(a) Dizziness
(b) Headache
(c) Sedation
(d) Also associated with priapism

(4) Drug interactions: major CYP 3A4 substrate

d. Venlafaxine (Effexor)

(1) Mechanism of action (serotonin-norepinephrine reuptake inhibitor (SNRI)

(a) Potent inhibitor of serotonin reuptake
(b) Inhibits norepinephrine at higher doses

(2) Usual adult dose: maximum 225–375 mg daily (immediate release), given in 2-3 divided doses
(3) Adverse effects

(a) May cause increased sweating
(b) Increased blood pressure

(4) Drug interactions: major CYP 2D6 substrate

e) Mirtazapine (Remeron)

(1) Mechanism of action: central presynaptic alpha-2 adrenergic antagonist effects, which thereby increases release of serotonin and norepinephrine
(2) Dose

(a) Usual adult dose: Starting dose is 15 mg, with a dosage range of 15–30 mg per day
(b) Taken at bedtime

(3) Adverse effects: may cause drowsiness and weight gain
(4) Drug interactions

(a) Major CYP 1A2, 2D6, 3A4 substrate
(b) Avoid with MAOI

B. Bipolar disorder

1. Bipolar: elevated mood with or without periods of major depressive disorder

a. Bipolar I: classic mania, majority also have major depressive disorder
b. Bipolar II: do not meet criteria for manic episode; have a milder form called hypomania, interspersed with major depressive disorder

2. Etiology

a. Exact cause is unknown

3. Signs and symptoms

a. Usually begins with an acute phase of symptoms followed by a course of relapse and remission
b. Episodes are manic, depressive, hypomanic, or a combination

4. Diagnosis is based on signs and symptoms
5. Treatment

a. Mood stabilizers
b. Lithium

(1) Mechanism of action: alters cation transport across cell membrane in nerve and muscle cells
(2) Onset of action: 4- to 10-day latency period
(3) Usual adult dose

(a) Initial dose of lithium is 300 mg two or three times daily
(b) May increase dose every 4 to 5 days based on levels
(c) Maintenance dose 900–1200 mg daily

(4) Target blood level for acute phase management: between 0.8 and 1.2 meq/L; maintenance levels: 0.6–1.2 meq/L
(5) Monitor blood urea nitrogen (BUN), serum creatinine (SCr), thyroid function
(6) Adverse effects

(a) Polyuria
(b) Tremor
(c) Loose stools
(d) Cognitive side effects
(e) Weight gain

(7) Longer term complications

(a) Renal impairment
(b) Cardiac rhythm disturbances
(c) Hypothyroidism

(8) Drug interactions

(a) Drugs that may increase lithium levels: thiazide diuretics, NSAID, Angiotensin converting enzyme (ACE) inhibitors
(b) Drugs that may decrease lithium levels: potassium-sparing diuretics
(c) Drugs that may increase or decrease lithium levels: loop diuretics, calcium channel blockers

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