Download General classes of disorders

Fifth stage
‫الهام الجماس‬.‫د‬
Psychiatry
Lec-12
3/12/2016
Psychotropic drugs
Psychotropic drugs
Treat mood, cognition, and behavioral disturbances associated with psychological disorders
Most are not used recreationally or abused; Benzodiazepines are the exception
General classes of disorders
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Mood
Anxiety
Psychotic
Other Disorders
Attention Deficit Disorder
Depression
Depression is a serious disorder that afflicts approximately 14 million adults in the United
States each year. The lifetime prevalence rate of depression in the United States has been
estimated to include 16 percent of adults (21 percent of women, 13 percent of men), or
more than 32 million people
Antidepressants
Indications:
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Unipolar and bipolar depression,
organic mood disorders,
schizoaffective disorder,
anxiety disorders including OCD, panic, social phobia, PTSD,
premenstrual dysphoric disorder
impulsivity associated with personality disorders.
General guidelines
Antidepressant efficacy is similar so selection is based on past history of a response, side
effect profile and coexisting medical conditions.
There is a delay typically of 3-6 weeks after a therapeutic dose is achieved before symptoms
improve.
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If no improvement is seen after a trial of adequate length (at least 2 months) and adequate
dose, either switch to another antidepressant or augment with another agent.
Mood disorders/Antidepressants
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MAO Inhibitors
Tricyclics
Selective Serotonin Reuptake Inhibitors
Dual Action Antidepressants
Selective Norepinephrine Reuptake Inhibitors
Atypical antidepressant
Mood Stabilizers (Antimanic
Agents)
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LithiumCarbonate
Valproic Acid
Carbamazepine
Lamotragine
Topirimate
MAOI
Use in late 1950s & ended in early 1960s
use ended due to side effect (death)
MAO breaks down many chemicals including tyramine
Tyramine is present in cheeses, red wines, alcohol, smoked fish
MAO in liver breaks down tyramine; Causes a hypertensive crisis "cheese syndrome"
increased blood pressure ➔ stroke ➔ death
increased heart rate ➔ heart attack ➔ death
Bind irreversibly to monoamine oxidase thereby preventing inactivation of biogenic amines
such as norepinephrine, dopamine and serotonin leading to increased synaptic levels.
They are very effective for depression
Side effects include orthostatic hypotension, weight gain, dry mouth, sedation, sexual
dysfunction and sleep disturbance
Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or
sympathomimetics.
Serotonin Syndrome can develop if take MAOI with meds that increase serotonin or have
sympathomimetic actions. Serotonin syndrome sx include abdominal pain, diarrhea,
sweats, tachycardia, HTN, myoclonus, irritability, delirium. Can lead to hyperpyrexia,
cardiovascular shock and death.
To avoid need to wait 2 weeks before switching from an SSRI to an MAOI. The exception of
fluoxetine where need to wait 5 weeks because of long half-life.
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Tricyclic antidepressants
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Act as agonists to catecholamines
No "cheese syndrome"
Side effects are the major problem
Cardiotoxic
Sedative action
Block acetylcholine system, especially muscarinic receptors
blurred vision, dry mouth, urinary retention, constipation, mental confusion
Block histamine receptors - sedation
Precaution
 Very effective but potentially unacceptable side effect profile i.e. antihistaminic,
anticholinergic, antiadrenergic
 Lethal in overdose (even a one week supply can be lethal!)
 Can cause QT lengthening even at a therapeutic serum level
TCA
Have tertiary amine side chains
Side chains are prone to cross react with other types of receptors which leads to more side
effects including antihistaminic (sedation and weight gain), anticholinergic (dry mouth, dry
eyes, constipation, memory deficits and potentially delirium), antiadrenergic (orthostatic
hypotension, sedation, sexual dysfunction)
Act predominantly on serotonin receptors
Examples:Imipramine, amitriptyline, doxepin, clomipramine
Selective serotonin reuptake inhibitors SSRI
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Selectively block re-uptake of 5-HT
Work on DA and NE as well but very little
Eliminate ACh and antihistamine effects
No more effective than MAOIs or tricyclics
Better because there are fewer side effects
On market since late 1980s & early 1990s
Fluoxetine – Prozac
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Sertraline - Zoloft
Paroxetine - Paxil
Fluvoxamine - Luvo
Citalopram - Celexa
Escitalopram - Lexapro
Block the presynaptic serotonin reuptake
Treat both anxiety and depressive
Most common side effects include GI upset, sexual dysfunction (30%+!), anxiety,
restlessness, nervousness, insomnia, fatigue or sedation, dizziness
Very little risk of cardiotoxicity in overdose
Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and
dysphoria
SNRI
Selectively inhibits NE transporter.
Blocks re-uptake.
 Atomoxetine (Strattera)
 Reboxetine (Edronax, Vestra)
Dual action AD
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Affinity for both 5-HT and NE.
Block re-uptake for both
In this sense, like TCAs
Duloxetine - Cymbalta
Atypical Antidepressants
The atypical antidepressants are a mixed group of agents that have actions at several
different sites. This group includes bupropion; mirtazapine; nefazodone, and trazodone
Bupropion (Wellbutrin)
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No effect on either 5-HT or NE
Effective at blocking DA reuptake
May be similar action to cocaine
Lowers seizure threshold
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Venlafaxine (Effexor)
5-HT, DA and NE reuptake blocker
Drugs for bipolar
Treat the manic phases of Bipolar Disorder
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Lithium
Valproic Acid
Carbamazepine/Oxcarbazepine
Lamotragine
Topirimate
Symbyax – Combo of olanzepine and fluoxetine (Zyprexa & Prozac)
Mood Stabilizers
Indications: Bipolar, cyclothymia, schizoaffective, impulse control and intermittent
explosive disorders.
Classes: Lithium, anticonvulsants, antipsychotics
Which you select depends on what you are treating and again the side effect profile.
Lithium
 Only medication to reduce suicide rate.
 Rate of completed suicide in BAD ~15%
 Effective in long-term prophylaxis of both mania and depressive episodes in 70+% of
BAD I pts
 Factors predicting positive response to lithium
 Prior long-term response or family member with good response
 Classic pure mania
 Mania is followed by depression
Before starting :Get baseline creatinine, TSH and CBC. In women check a pregnancy testduring the first trimester is associated with Ebstein’s anomaly 1/1000 (20X greater risk than
the general population)
Monitoring: Steady state achieved after 5 days- check 12 hours after last dose. Once stable
check q 3 months and TSH and creatinine q 6 months.
Goal: blood level between 0.6-1.2mmol /lit
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Lithium side effects
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Most common are GI distress including reduced appetite, nausea/vomiting, diarrhea
Thyroid abnormalities
Non significant leukocytosis
Polyuria/polydypsia secondary to ADH antagonism. In a small number of patients can
cause interstitial renal fibrosis.
 Hair loss, acne
 Reduces seizure threshold, cognitive slowing, intention tremor
Lithium toxicity
Mild- levels 1.5-2.0 see vomiting, diarrhea, ataxia, dizziness, slurred speech, nystagmus.
Moderate-2.0-2.5 nausea, vomiting, anorexia, blurred vision, clonic limb movements,
convulsions, delirium, syncope
Severe- >2.5 generalized convulsions, oliguria and renal failure
Study Questions
Choose the ONE best answer.
12.1 A 55-year-old teacher began to experience changes in mood. He was losing interest in
his work and lacked the desire to play his daily tennis match. He was preoccupied with
feelings of guilt, worthlessness, and hopelessness. In addition to the psychiatric symptoms,
the patient complained of muscle aches throughout his body. Physical and laboratory tests
were unremarkable. After 6 weeks of therapy with fluoxetine, the patient's symptoms
resolved. However, the patient complains of sexual dysfunction. Which of the following
drugs might be useful in this patient?
A. Fluvoxamine.
B. Sertraline.
C. Citalopram.
D. Mirtazapine.
E. Lithium.
Correct answer = D. Sexual dysfunction commonly occurs with TCAs, SSRIs, and SNRIs.
Mirtazapine is largely free from sexual side effects.
A 25-year-old woman has a long history of depressive symptoms accompanied by body
aches. Physical and laboratory tests are unremarkable. Which of the following drugs might
be useful in this patient?
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A. Fluoxetine.
B. Sertraline.
C. Phenelzine.
D. Mirtazapine.
E. Duloxetine.
Correct answer = E. Duloxetine is an SNRI that can be used for depression accompanied by
neuropathic pain. MAOs and SSRIs have little activity against neuropathic pain
A 51-year-old woman with symptoms of major depression also has narrow-angle glaucoma.
Which of the following antidepressants should be avoided in this patient?
A. Amitriptyline.
B. Sertraline.
C. Bupropion.
D. Mirtazepine.
E. Fluvoxamine.
Correct answer = A. Because of its potent antimuscarinic activity, amitriptyline should not
be given to patients with glaucoma because of the risk of acute increases in ocular
pressure. The other antidepressants all lack antagonist activity at the muscarinic receptor.
A 36-year-old man presents with symptoms of compulsive behavior. If anything is out of
order, he feels that “work will not be accomplished effectively or efficiently.― He
realizes that his behavior is interfering with his ability to accomplish his daily tasks but
cannot seem to stop himself. Which of the following drugs would be most helpful to this
patient?
A. Imipramine.
B. Fluvoxamine.
C. Amitriptyline.
D. Tranylcypromine.
E. Lithium.
Correct answer = B. Selective serotonin reuptake inhibitors are particularly effective in
treating obsessive-compulsive disorder; flu vox amine is approved for this condition. The
other drugs are ineffective in the treatment of obsessive-compulsive disorder.
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