PSYCHOSIS

Submitted by:
17-M-14
34-M-14
44-M-14
65-M-14
70-M-14
PSYCHOSIS
 Psychosis is a symptom, not an illness. A mental
or physical illness, substance abuse, or extreme
stress or trauma can cause it.
 You may have depression, anxiety, and sleep
problems, too. It could be a struggle just to get
through your day.
 You might also feel paranoid, experience
hallucinations, have trouble expressing ideas, or
slack off in your personal hygiene.
causes
 Doctors do not know exactly what causes
psychosis.
 In some people who have a biological
vulnerability to developing psychosis, it may be
triggered by too little sleep, some prescription
medications, and abuse of alcohol or drugs like
marijuana and LSD.
 Traumatic events, like the death of a loved one or
sexual assault, can lead to psychosis in people
who are vulnerable to it
 So can traumatic brain injuries, brain tumors,
strokes, Parkinson’s disease, and Alzheimer’s
disease.
Psychiatric disorders
 Anxiety disorders
 Bipolar disorders
 Major depressive disorder
 Schizophrenia
 Sleep-wake disorders
 Substance related disorders
ANXIETY DISORDERS
 Types of Anxiety disorders
 Generalized anxiety disorder (GAD)
 Panic disorder
 Social anxiety disorder (SAD)
 Post traumatic stress disorder
(PTSD)
CLINICAL PRESENTATION
Generalized anxiety disorder (GAD)

Women are twice as likely as men to have GAD. The illness has a gradual
onset at an average age of 21 years.
Panic disorder
 Recurrent unexpected panic attacks. At least one attack has been followed by
at least one month of one: 1) persistent worry about additional panic attacks
or 2) change in behavior related to the attacks.
 Symptoms reach a peak within 10 minutes and usually last no more than 20 or
30 minutes.
 Social anxiety disorder (SAD)
 SAD is a chronic disorder with an intense fear or anxiety about one or more
social situations in which there is scrutiny by others which may result in negative
evaluation and rejection.
 The fear or avoidance lasts for at least 6 months and causes significant
impairment in functioning.
 Post traumatic stress disorder (PTSD)
 In adults and children older than 6, there is exposure to actual or threatened
death, serious injury, or sexual violence, either directly, or by witnessing the
event(s) happening to others, learning about the event(s) happening to someone
close, or experiencing repeated or extreme exposure to details of the event(s).
 Symptoms (Table 66–4) must be present longer than 1 month.
Diagnosis
 Treatment
Generalized anxiety disorder (GAD)
 Goals of Treatment: The goals are to reduce severity, duration, and frequency of symptoms and
improve functioning. The long-term goal is minimal or no anxiety symptoms, no functional
impairment, prevention of recurrence, and improved quality of life.
 Nonpharmacologic modalities include psychotherapy, short-term counseling, stress management,
cognitive therapy, meditation, supportive therapy, and exercise. Ideally, patients with GAD should
have psychological therapy, alone or in combination with anti anxiety drugs.
Panic disorder
 Goals of Treatment: The goals are complete resolution
of panic attacks, marked reduction in anticipatory
anxiety, elimination of phobic avoidance, and
resumption of normal activities.
 General Approach
 Educate patient to avoid caffeine, nicotine, alcohol,
drugs of abuse, and stimulants.
 If pharmacotherapy is used, antidepressants, especially
the SSRIs, are preferred in elderly patients and youth.
The benzodiazepines are second line in these patients
because of potential problems with disinhibition.
 Usually patients are treated for 12 to 24 months
before discontinuation is attempted over 4 to 6
months.
FIGURE 66–1. Algorithm for the
pharmacotherapy of panic disorder.
Social anxiety disorder
 Goals of Treatment: The goals are to reduce the
physiologic symptoms and phobic avoidance, increase
participation in desired social activities, and improve
quality of life.
 Patients with SAD often respond more slowly and
less completely than patients with other anxiety
disorders.
 After improvement, at least 1 year of maintenance
treatment is recommended. Long term treatment may
be needed for patients with unresolved symptoms,
comorbidity, an early onset of disease, or a prior
history of relapse.
FIGURE 66–2. Algorithm for the pharmacotherapy of generalized social anxiety
disorder.
 Post traumatic stress disorder (PTSD)
Goals of Treatment: The goals are to decrease core symptoms, disability,
and comorbidity and improve quality of life.
Bipolar disorder
Introduction
 Bipolar I disorder: at least one manic episode,
which may have been preceded by and may be
followed by hypomanic or major depressive
episodes.
 Bipolar II disorder: at least one hypomanic
episode and a current or past major depressive
episode.
PATHOPHYSIOLOGY
Medical conditions, medications, and treatments
that may induce mania are shown in Table 67–1.
CLINICAL PRESENTATION
Different types of episodes may occur
sequentially with or without a period of normal mood
(euthymia) between.
Major Depressive Episode
Delusions, hallucinations, and suicide attempts are
more common in bipolar depression than in unipolar
depression.
Manic Episode
 Acute mania usually begins abruptly, and symptoms increase
over several days. Bizarre behavior, hallucinations, and
paranoid or grandiose delusions may occur. There is marked
impairment in functioning.
 Manic episodes may be precipitated by stressors, sleep
deprivation, antidepressants, central nervous system (CNS)
stimulants, or bright light.
HYPOMANIC EPISODE
There is no marked impairment in social
or occupational functioning, no delusions,
and no hallucinations. Some patients may
be more productive than usual, but 5% to
15% of patients may rapidly switch to a
manic episode.
Goals of treatment:
Treatment
General approach
NONPHARMACOLOGIC
THERAPY
Nonpharmacologic approaches include:
1) psychotherapy (eg, individual, group, and family),
interpersonal therapy, and/or cognitive behavioral therapy,
2) stress reduction techniques, relaxation therapy, massage, and
yoga,
3) sleep (regular bedtime and awake schedule; avoid alcohol or
caffeine intake prior to bedtime),
4) nutrition (regular intake of protein-rich foods or drinks and
essential fatty acids; supplemental vitamins and minerals), and
5) exercise (regular aerobic and weight training at least three
times a week).

PHARMACOLOGIC THERAPY
MAJOR DEPRESSIVE DISORDER
Major Depressive disorder
 The essential feature of major depressive disorder is a clinical course
characterized by one or more major depressive episodes without a
history of manic or hypomanic episodes.
CLINICAL PRESENTATION
 Emotional symptoms: diminished ability to experience pleasure, loss
of interest in usual activities, sadness, pessimism, crying,
hopelessness, anxiety (present in ~90% of depressed outpatients),
guilt, and psychotic features (eg, auditory hallucinations and
delusions).
 Physical symptoms: fatigue, pain (especially headache), sleep
disturbance, decreased or increased appetite, loss of sexual interest,
and gastrointestinal (GI) and cardiovascular complaints (especially
palpitations).
 Intellectual or cognitive symptoms: decreased ability to concentrate
or slowed thinking, poor memory for recent events, confusion, and
indecisiveness.
 Psychomotor disturbances: psychomotor retardation (slowed physical
movements, thought processes, and speech) or psychomotor agitation.
DIAGNOSIS
 Major depressive disorder is characterized by one or more major
depressive episodes , as defined by the Diagnostic and Statistical
Manual of Mental Disorders, 5th ed.
 Five or more of the following must have been present nearly every
day during the same 2-week period and cause significant distress
or impairment:
 Depressed mood;
 Diminished interest in almost all activities;
 Weight loss or gain;
 Insomnia or hypersomnia;
 Psychomotor agitation or retardation;
 Fatigue or loss of energy;
 Feelings of worthlessness or excessive guilt;
 Diminished concentration or indecisiveness;
 Recurrent thoughts of death, suicidal ideation without a specific plan,
suicide attempt, or a plan for committing suicide.
Continue..
 The depressive episode must not be attributable to
physiological effects of a substance or medical
condition. Lastly, there must not be a history of
manic-like or hypomanic-like episodes unless they
were induced by a substance or medical condition.
 Diagnosis requires a medication review, physical
examination, mental status examination, a complete
blood count with differential, thyroid function tests,
and electrolyte determinations.
 Many chronic illnesses and substance abuse and
dependence disorders are associated with
depression. Medications associated with depression
include many antihypertensives, oral contraceptives,
isotretinoin, interferon-β1a, and many others.
TREATMENT
 Goals of Treatment: The goals are to reduce
symptoms of depression, minimize adverse effects,
ensure adherence to the prescribed regimen,
facilitate return to premorbid functioning, and
prevent further depressive episodes.
NONPHARMACOLOGIC TREATMENT:
 Psychotherapy may be first-line therapy for mild to
moderately severe major depressive episode. The
efficacy of psychotherapy and antidepressants is
considered to be additive.
 Psychotherapy alone is not recommended for acute
treatment of severe and/or psychotic major
depressive disorder.
Continue..
 Electroconvulsive therapy (ECT) is a safe and effective
treatment for major depressive disorder. It is considered
when a rapid response is needed, risks of other
treatments outweigh potential benefits, there is history
of a poor response to drugs, and the patient prefers
ECT. A rapid therapeutic response (10–14 days) has
been reported.
 Repetitive transcranial magnetic stimulation has
demonstrated efficacy and does not require anesthesia
as does ECT.
 PHARMACOLOGIC THERAPY
General Approach:

 Figure 68–1 shows an algorithm for treatment of uncomplicated major depressive

General approach
 In general, antidepressants are equal in efficacy in groups of patients when administered in
comparable doses.
 Choice of antidepressant is influenced by the patient’s or family member’s history of
response, concurrent medical conditions, presenting symptoms, potential for drug– drug
interactions, side effect profiles, patient preference, and drug cost.
 Between 65% and 70% of patients with major depression improve with drug therapy.
 Psychotically depressed individuals generally require either ECT or combination therapy
with an antidepressant and antipsychotic.
 A 6-week trial of an antidepressant at maximum dosage is considered an adequate trial of
that medication.
 The acute phase of treatment lasts 6 to 12 weeks, and the goal is remission (ie, absence of
symptoms). The continuation phase (4–9 months after remission) seeks to
eliminate residual symptoms or prevent relapse. The maintenance phase (12–36
months or more) has a goal to prevent recurrence of a new episode of depression.
 Give elderly patients one half of the initial dose given to younger adults, and increase the
dose more slowly. The elderly may require 6 to 12 weeks of treatment to achieve the
desired antidepressant response.
 Some clinicians recommend lifelong therapy for persons younger than 40 years with two
or more prior episodes and for all persons with three or more prior episodes.
 Educate patients and their support systems about the delay in antidepressant response
(typically 2–4 weeks) and the importance of adherence before starting therapy and
throughout treatment.
Adverse effects
Drug–Drug Interactions
 TCAs may interact with other drugs that modify hepatic cytochrome
P450 (CYP450) enzyme activity or hepatic blood flow. TCAs also are
involved in interactions through displacement from protein-binding
sites.
 Increased plasma concentrations of TCAs and symptoms of toxicity
may occur when fluoxetine and paroxetine are added.
 The very slow elimination of fluoxetine and norfluoxetine makes it
critical to ensure a 5-week washout after fluoxetine discontinuation
before starting an MAOI. Potentially fatal reactions may occur when
any SSRI or TCA is co administered with an MAOI. TCAs and MAOIs
can be combined in refractory patients by experienced clinicians with
careful monitoring.
 Combining an SSRI with another 5-HT augmenting agent can lead to
the serotonin syndrome.
 The ability of any antidepressant to inhibit or induce the CYP450
enzymes can be a significant factor in determining its capability to
cause a pharmacokinetic drug–drug interaction. If an SSRI is added to a
regimen which includes drugs known to interact with SSRIs, the SSRI
starting dose should be low and slowly titrated.
SPECIAL POPULATIONS
Elderly Patients
 In the elderly, depressed mood may be less prominent than other
symptoms, such as loss of appetite, cognitive impairment,
sleeplessness, fatigue, physical complaints, and loss of interest and
enjoyment in usual activities.
 The SSRIs are often considered first-choice antidepressants in
elderly patients.
 Bupropion, venlafaxine, and mirtazapine are also effective and
well tolerated.
Pediatric Patients
 Symptoms of depression in childhood include boredom, anxiety,
failing adjustment, and sleep disturbance.
 Data supporting efficacy of antidepressants in children and
adolescents are sparse. Fluoxetine is the only FDA approved
antidepressant for treating depression in patients below 18 years
of age.
SLEEP- WAKE DISORDERS
Sleep- wake disorders
Category of Sleep-Wake disorders encompasses:
 insomnia,
 hypersomnolence,
 narcolepsy,
 breathing related sleep disorders,
 circadian rhythm sleep-wake disorders,
 non-rapid eye movement (NREM) sleep arousal disorders,
 nightmare disorder,
 rapid eye movement (REM) sleep behavior disorder,
 Restless legs syndrome,
 and substance/medication induced sleep disorder.
 Sleep physiology
 Humans typically have four to six cycles of non–rapid eye movement (NREM)
and REM sleep each night, each cycle lasting 70 to 120 minutes. Usually
there is progression through the four stages of NREM sleep before the first
REM period.
 Stage 1 of NREM is the stage between wakefulness and sleep. Stages 3 and 4
sleep are called delta sleep (i.e., slow-wave sleep).
 In REM sleep, there is a low-amplitude, mixed-frequency
electroencephalogram, increased electric and metabolic activity, increased
cerebral blood flow, muscle atonia, poikilothermia, vivid dreaming, and
fluctuations in respiratory and cardiac rate.
 The elderly have lighter more fragmented sleep with more arousals and
gradual reduction in slow-wave sleep.
 REM sleep is turned on by cholinergic cells. Dopamine has an alerting effect.
Neurochemicals involved in wakefulness include norepinephrine and
acetylcholine in the cortex and histamine and neuropeptides (eg, substance
P and corticotropin releasing factor) in the hypothalamus.
 Polysomnography (PSG) measures multiple electrophysiologic parameters
simultaneously during sleep (eg, electroencephalogram, electrooculogram,
and electromyogram) to characterize sleep and diagnose sleep disorders.
INSOMNIA
Clinical presentation and diagnosis
 Patients with insomnia complain of difficulty falling asleep,
maintaining sleep, or experiencing nonrestorative sleep.
 Transient (two or three nights) and short-term (<3 weeks) insomnia
is common and is usually related to a precipitating factor. Chronic
insomnia (>1 month) may be related to medical or psychiatric
disorders or medication, or it may be psychophysiologic.
 Causes of insomnia include stress; jet lag or shift work; pain or
other medical problems; mood or anxiety disorders; substance
withdrawal; stimulants, steroids, or other medications.
 In patients with chronic disturbances, a diagnostic evaluation
includes physical and mental status examinations, routine
laboratory tests, and medication and substance abuse histories.
TREATMENT
Goals of Treatment: Correct the underlying sleep
complaint, improve daytime functioning, and avoid
adverse drug effects.
General Approach
Behavioral and educational interventions that may
help include short-term cognitive behavioral
therapy, relaxation therapy, stimulus control
therapy, cognitive therapy, sleep restriction,
paradoxical intention, and sleep hygiene education
(Table 70–1)
Management
 Management includes identifying the cause of insomnia, educating
about sleep hygiene, managing stress, monitoring for mood
symptoms, and eliminating unnecessary pharmacotherapy.
 Transient and short-term insomnia should be treated with good
sleep hygiene and careful use of sedative-hypnotics if necessary.
Chronic insomnia calls for careful assessment for a medical cause,
nonpharmacologic treatment, and careful use of sedative-hypnotics
if necessary.
 Antihistamines (eg, diphenhydramine, doxylamine, and
pyrilamine) are less effective than benzodiazepines, but side
effects are usually minimal.
 The antidepressants are good alternatives for patients who should
not receive benzodiazepines, especially those with depression or a
history of substance abuse.
 Amitriptyline, doxepin, and nortriptyline are effective, but
side effects include anticholinergic effects, adrenergic blockade,
and cardiac conduction prolongation.
 Continue..
 Trazodone, 25 to 100 mg, is often used for insomnia induced by
selective serotonin reuptake inhibitors or bupropion and in patients
prone to substance abuse. Side effects include serotonin syndrome
(when used with other serotonergic drugs), oversedation, α-adrenergic
blockade, dizziness, and, rarely, priapism.
 Ramelteon is a melatonin receptor agonist selective for the MT1 and
MT2 receptors. The dose is 8 mg at bedtime. It is well tolerated, but side
effects include headache, dizziness, and somnolence. It is not a
controlled substance. It is effective for patients with chronic obstructive
pulmonary disease and sleep apnea.
 Valerian, a herbal product, is available without a prescription. The
recommended dose is 300 to 600 mg. It may cause daytime sedation.
 The benzodiazepine receptor agonists are the most commonly used
drugs for insomnia. They carry a caution regarding anaphylaxis, facial
angioedema, complex sleep behaviors (eg, sleep driving, phone calls, and
sleep eating). They include the newer nonbenzodiazepine γ-
aminobutyric acidA (GABAA) agonists and the traditional
benzodiazepines, which also bind to GABAA (Table 70–2).
 Nonbenzodiazepine GABAA Agonists
 In general, the nonbenzodiazepine hypnotics do not have significant active
metabolites, and they are associated with less withdrawal, tolerance, and rebound
insomnia than the benzodiazepines.
 Zolpidem has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It
is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on
sleep stages. Its duration is approximately 6 to 8 hours. Common side effects are
drowsiness, amnesia, dizziness, headache, and gastrointestinal (GI) complaints.
Rebound effects when discontinued and tolerance with prolonged use are minimal,
but theoretical concerns about abuse exist. It appears to have minimal effects on next
day psychomotor performance. The usual dose is 5 mg in women, the elderly, and
those with liver impairment, and 5 to 10 mg in men. Sleep eating has been reported. It
should be taken on an empty stomach.
 Zaleplon has a rapid onset, a half-life of ~1 hour, and no active metabolites. It also
binds to the GABAA receptor. It does not reduce nighttime awakenings or increase the
total sleep time. It does not appear to cause significant rebound insomnia or next-day
psychomotor impairment. The most common side effects are dizziness, headache, and
somnolence. The recommended dose is 10 mg (5 mg in the elderly).
 Eszopiclone has a rapid onset and duration of action of up to 6 hours. The most
common adverse effects are somnolence, unpleasant taste, headache, and dry mouth.
It may be taken nightly for up to 6 months.
Benzodiazepine Hypnotics
 The pharmacokinetics and dosing of benzodiazepine
receptor agonists are summarized in Table 70–2.
 Benzodiazepines have sedative, anxiolytic, muscle
relaxant, and anticonvulsant properties. They increase
stage 2 sleep and decrease REM and delta sleep.
 Overdose fatalities are rare unless benzodiazepines
are taken with other CNS depressants.
 Triazolam is distributed quickly because of its high
lipophilicity and thus has a short duration of effect.
Erythromycin, nefazodone, fluvoxamine, and
ketoconazole reduce the clearance of triazolam and
increase plasma concentrations.
 The effects of flurazepam and quazepam are long
because of active metabolites.
Benzodiazepine adverse effects
 Side effects include drowsiness, psychomotor incoordination,
decreased concentration, cognitive deficits, and anterograde
amnesia which is minimized by using the lowest dose possible.
 Tolerance to daytime CNS effects (eg, drowsiness, decreased
concentration) may develop in some individuals.
 Tolerance to hypnotic effects develops after 2 weeks of continuous
use of triazolam. Efficacy of flurazepam, quazepam, and
temazepam lasts for at least 1 month of nightly use.
Estazolam reportedly maintains efficacy at maximum
dosage for up to 12 weeks.
 Rebound insomnia occurs frequently with high doses of
triazolam, even when used intermittently.
 Rebound insomnia is minimized by using the lowest effective dose
and tapering the dose upon discontinuation.
 Long elimination half-life benzodiazepines are associated with falls
and hip fractures; thus, flurazepam, and quazepam should be
avoided in the elderly.
 SLEEP APNEA

Apnea is repetitive episodes of cessation

of breathing during sleep.
OBSTRUCTIVE SLEEP APNEA
 Obstructive sleep apnea (OSA) is potentially life threatening
and characterized by repeated episodes of nocturnal
breathing cessation. It is caused by occlusion of the upper
airway, and blood oxygen (O2) desaturation can occur.
Episodes may be caused by obesity or fixed upper airway
lesions, enlarged tonsils, amyloidosis, and hypothyroidism.
Complications include arrhythmias, hypertension, cor
pulmonale, and sudden death.
 Heavy snoring, severe gas exchange disturbances, respiratory
failure, and gasping occur in severe episodes. Patients with
OSA usually complain of excessive daytime sleepiness. Other
symptoms are morning headache, poor memory, and
irritability.
 The apneic episode is terminated by a reflex action in
response to the fall in blood O2 saturation that causes an
arousal with resumed breathing.
Treatment
 Goal of Treatment:
The goal is alleviate sleep-disordered breathing (Fig. 70–1).
 Nonpharmacologic approaches are the treatments of choice
(eg, weight loss [for all overweight patients], tonsillectomy,
nasal septal repair, and nasal positive airway pressure [PAP],
which may be continuous or bilevel). Other surgical therapies,
such as uvulopalatopharyngoplasty and tracheostomy, may be
necessary in severe cases.
 Management parameters are published by the American
Academy of Sleep Medicine. Avoid of all CNS depressants and
drugs that promote weight gain. Angiotensin converting
enzyme (ACE) inhibitors can also worsen sleep-disordered
breathing.
 Modafinil and armodafinil are approved by the FDA to
improve wakefulness in those with residual daytime
sleepiness. They should be used only in patients without
cardiovascular disease who are using optimal PAP therapy.
CENTRAL SLEEP APNEA
 Central sleep apnea (CSA), less frequent than OSA, is
characterized by repeated episodes of apnea caused
by temporary loss of respiratory effort during sleep.
 It may be caused by autonomic nervous system
lesions, neurologic diseases, high altitudes, opioid
use, and congestive heart failure.
Treatment
 PAP with or without supplemental O2 improves CSA.
 Acetazolamide causes metabolic acidosis that
stimulates respiratory drive and may be beneficial
for high altitude, heart failure, and idiopathic CSA.
NARCOLEPSY
 Essential features are sleep attacks, cataplexy,
hypnagogic and hypnopompic hallucinations, and
sleep paralysis. Patients complain of excessive
daytime sleepiness, sleep attacks that last up to 30
minutes, fatigue, impaired performance, and
disturbed nighttime sleep.
 Cataplexy, which occurs in 70% to 80% of
narcoleptics, is sudden bilateral loss of muscle
tone with collapse. It is often precipitated by
highly emotional situations.
 The hypocretin/orexin neurotransmitter system
may play a central role in narcolepsy. An
autoimmune process may cause destruction of
hypocretin-producing cells.
 TREATMENT
 Goals of Treatment: The goal is to maximize alertness during waking hours and
improve quality of life (Fig. 70–1). Encourage good sleep hygiene and two or more
daytime naps daily (as little as 15 min).
 Pharmacotherapy (Table 70–3) focuses on excessive daytime sleepiness and REM
sleep abnormalities
 Modafinil, the standard for treatment of excessive daytime sleepiness, and
armodafinil (the active R-isomer) are FDA approved. Evidence suggests no risk of
tolerance, withdrawal, or risk of abuse. Side effects of modafinil include headache,
nausea, nervousness, and insomnia.
 Amphetamines and methylphenidate have a fast onset of effect and durations of 3
to 4 hours and 6 to 10 hours, respectively, for excessive daytime sleepiness.
Amphetamines have more risk of abuse and tolerance. Side effects include insomnia,
hypertension, palpitations, and irritability.
 The most effective treatments for cataplexy are the tricyclic antidepressants,
fluoxetine, or venlafaxine. Imipramine, protriptyline, clomipramine, fluoxetine, and
nortriptyline are effective in approximately 80% of patients. Selegiline improves
hypersomnolence and cataplexy.
 Sodium oxybate (γ-hydroxybutyrate; a potent sedative-hypnotic) improves
excessive daytime sleepiness and decreases episodes of sleep paralysis, cataplexy,
and hypnagogic hallucinations. Give at bedtime and repeat 2.5 to 4 hours later. Side
effects include nausea, somnolence, confusion, dizziness, and incontinence.
References
 Pharmacotherapy Handbook Ninth
Edition, Barbara G. Wells,