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PsychopharmacologyGreg Matthew Teo (MD080087)ASMPH 2013 YL8
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OutlineI. Basic Biologic PrinciplesII. Psychosis and Schizophrenic
DisordersIII.Mood DisordersIV.Anxiety Disorders
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I. BASIC BIOLOGIC PRINCIPLES
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Neurotransmitter – chemical signals that flow between neurons
• The molecule is synthesized in the neuron.• The molecule is present in the presynaptic
neuron and is released on depolarization in physiologically significant amounts.• When administered exogenously as a drug, the
exogenous molecule mimics the effects of the endogenous neurotransmitter.• A mechanism in the neurons or the synaptic cleft
acts to remove or deactivate the neurotransmitter.
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II. PSYCHOSIS AND SCHIZOPHRENIC DISORDERS
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Pathophysiology: Dopamine Hypothesis• Dopaminergic hyperactivity linked to severity of
POSITIVE psychotic symptoms• Proposed mechanisms:• Too much release of dopamine• Too many dopamine receptors• Hypersensitivity of dopamine receptors
• No specified dopamine tract although MESOCORTICAL and MESOLIMBIC tracts are most often implicated
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4 Dopaminergic Pathways
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Dopaminergic Pathways in PSYCHOSIS• Mesocortical Dopaminergic Pathway• Involves the prefrontal cortex• Predominance of D1 receptors• HYPOACTIVITY results to negative symptoms
• Mesolimbic Dopaminergic Pathway• Involves the limbic system• Predominance of D2 receptors• HYPERACTIVITY results to positive symptoms
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Other hypotheses for Schizophrenia
• Serotonin excess causes both positive and negative symptoms in schizophrenia• Neuronal degeneration within the
norepinephrine reward neural system can cause ANHEDONIA• Loss of inhibitory GABAergic neurons can lead to
hyperactivity of dopaminergic neurons
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A. TYPICAL ANTIPSYCHOTICS (DOPAMINE RECEPTOR ANTAGONISTS)
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Class Examples Potency
PHENOTHIAZINES
Aliphatic Chlorpromazine (Thorazine)
Low potency
Piperazine Fluphenazine (Permitil)Thioridazine (Mellaril)
High potencyLow-potency
THIOXANTHENES Thiothixene (Navane) High-potency
DIHYDROINDOLE Molindone (Moban) High-potency
BUTYROPHENONES Haloperidol (Haldol) High potency
• Low-potency drugs – given in doses of several hundred milligrams per day; produce MORE WEIGHT GAIN and SEDATION• High-potency drugs – less than 10 mg per day;
more likely to cause EXTRAPYRAMIDAL SYMPTOMS
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Typical Antipsychotics
• Mechanism of action for antipsychotic activity: high-affinity antagonism of DOPAMINE D2 receptors• Also block noradrenergic, cholinergic, and
histaminergic receptors• 1st mainstay treatment of schizophrenia during
the 1950s-1980s• No longer the mainstay of the treatment of
schizophrenia with the advent of ATYPICAL ANTIPSYCHOTICS
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• Therapeutic Effects on Schizophrenia:• Reduce both acute
psychotic symptoms and prevent future exacerbations• Most dramatic
effects against POSITIVE SYMPTOMS• May worsen
negative symptoms
• Indications • Acute psychotic episodes in
schizophrenia and schizoaffective disorder
• Maintenance treatment in schizophrenia and schizoaffective disorders
• Mania• Depression with psychotic
symptoms• Delusional disorder• Borderline personality disorder• Substance-induced psychotic
disorder• Delirium and dementia• Mental disorders due to a medical
condition• Childhood schizophrenia• Pervasive developmental disorder• Tourette's syndrome• Huntington's disease
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Side Effects:• Neurological• Acute extrapyramidal syndromes• Akathisia• Acute dystonia• Drug-induced parkinsonism• Neuroleptic malignant syndrome• Chronic extrapyramidal syndromes• Tardive dyskinesia and dystonia• Perioral tremor• Can lower the seizure threshold – Molindone is the
least epileptogenic
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Side Effects:
• Orthostatic (Postural) Hypotension• Cardiac – low-potency drugs cause prolongation of
QT and PR intervals, blunting of T waves and ST depression• Endocrine – breast enlargement, galactorrhea,
amenorrhea, inhibited orgasm in women and impotence in men• Peripheral Anticholinergic Effects • dry mouth and nose, blurred vision, constipation,
urinary retention, mydriasis, CONSTIPATION• WEIGHT GAIN not as severe as with atypicals
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B. ATYPICAL ANTIPSYCHOTICS (SEROTONIN-DOPAMINE ANTAGONISTS)
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Mechanism of Action• Higher ratio of serotonin type 2 (5HT2A) to D2
receptor blockade more specific for mesolimbic than striatal dopamine system reduced risk for EPS and tardive dyskinesia • Examples:• Risperidone (Risperdal)• Olanzapine (Zyprexa)• Quetiapine (Seroquel)• Clozapine (Clozaril)• Ziprasidone (Geodon)
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Indications
• Schizophrenia and Schizoaffective Disorder• Proven efficacy for treatment of positive
symptoms and clearly superior than DRAs for treatment of negative symptoms• Fewer relapses and less frequent hospitalizations
than DRAs• Acute Mania • Maintenance Treatment for Bipolar Disorder –
Olanzapine• Augment antidepressants in acute management of
Major Depression
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Risperidone (Risperdal)
• Dosage: 1-2 mg at night which can then be raised to 4 mg per day• Side effects: • Extrapyramidal effects are dosage
dependent• Weight gain, anxiety, nausea and
vomiting, rhinitis, erectile dysfunction, orgasmic dysfunction and increased pigmentation
• Only SDA currently available in depot formulation• 25, 50 or 75 mg IM every 2 weeks
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Olanzapine (Zyprexa)
• Dosages: starting daily dose of 5-10 mg raised to 10 mg a day• Side effects: • More frequent weight gain than
other atypical antipsychotics which plateaus after about 10 months and is not dose-related• Constipation, somnolence, dry
mouth, dizziness, dyspepsia, increased appetite, akathisia, tremor
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Quetiapine (Seroquel)
• Side effects:• Most common: somnolence,
postural hypotension, and dizziness• SDA to least likely cause
extrapyramidal side effects, regardless of dose
• Dosages:• 400 mg/day for Schizophrenia• 800 mg/day for mania• 300 mg/day for bipolar depression• 25-300 mg at night for insomnia
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Ziprasidone (Geodon)
• Also considered a serotonin-norepeinephrine reuptake inhibitor (SNRI)• Side effects:• No significant effects outside
the CNS • Almost no weight gain and no
prolactin elevation• BUT can cause QT prolongation
thus contraindicated in patients with arrythmias
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Clozapine (Clozaril)
• Not considered a first-line agent because of its side effects and need for weekly blood tests • Can cause agranulocytosis –
0.73% risk during the 1st year• Good for suicidality
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Aripiprazole (Abilify)
• Potent 5-HT2A antagonist but unlike other SDAs it is a partial D2 agonist• Competes with D2 receptors
for endogenous dopamine functional reduction of dopamine activity
• Usually nonsedating and has not been found to pose an increased risk of weight gain and diabetes
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C. PHASES OF TREATMENT
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Acute Psychosis
• lasts from 4-8 weeks• Typically associated with severe agitation• Goal: alleviate most severe psychotic symptoms• Give antipsychotics and benzodiazepines
• Single IM injection of haloperidol (Haldol), fluphenazine (Prolixin, Permitil), olanzapine (Zyprexa), or ziprasidone (Geodon) calming without excess sedation
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Stabilization and Maintenance Phase• Goal: prevent relapse and to assist patient in
improving their level of functioning• 16-23% of patients receiving treatment will
relapse within a year• 53-72% of patients without medications will
relapse within a year• Generally recommended that multiepisode
patients receive maintenance treatment for at least 5 years
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III. MOOD DISORDERS
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A. PHARMACOTHERAPY FOR MAJOR DEPRESSION
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Monoamine hypothesis of Depression• depression is related
to a deficiency in the amount or function of cortical and limbic serotonin (5-HT), norepinephrine (NE), and dopamine (DA).
Serotonin – Raphe Nuclei
Noradrenaline – locus ceruleus
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Acute Phase of Treatment
• Lasts a minimum of 6-12 weeks• Goals: induce remission of symptoms and
achieve a full return to the patient’s baseline level of functioning• Antidepressant medications can be used as an
initial treatment modality by patients with mild, moderate or severe MDD
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Acute Phase of Treatment
• Clinical Features that may suggest that medications are the preferred treatment:• History of prior positive response to
antidepressant medications• Presence of moderate to severe symptoms • Significant sleep or appetite disturbances• Agitation• Patient preference• Anticipation of the need for maintenance
therapy
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Choosing an Antidepressant Medication• No replicable or robust findings to
establish a clinically meaningful difference
• For most patients, the effectiveness of antidepressant medications is generally comparable between and within classes
• Antidepressant medications, however, do differ in their potential to cause particular side effects
• Optimal for most patients: SSRIs, SNRIs, mirtazapine, bupropion
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Continuation Phase
• To reduce the risk of relapse, patients who have been treated successfully with antidepressant medications in the acute phase should continue treatment with these agents for 4-9 months.• Depression-focused psychotherapy is
recommended.• Patients who respond to an acute course of ECT,
continuation pharmacotherapy with combination of lithium and nortriptyline has the best available evidence for efficacy.
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Maintenance Phase
• Antidepressant medication that produced symptom remission during the acute and continuation phase should be continued at a full therapeutic dose.• Indicated for patients who have had 3 or more
major depressive episodes or who have chronic major depressive disorder.
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SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)
Fluoxetine (Prozac)Sertraline (Zoloft)Paroxetine (Paxil)Fluvoxamine (Luvox)Citalopram (Celexa)Escitalopram (Lexapro)
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Pharmacodynamics• MOA: 5-HT reuptake inhibition• Citalopram and Escitalopram • Most selective with very little inhibition of
norepinephrine or dopamine reuptake and very low affinities for H1, GABA or benzodiazepine receptors
• Fluoxetine• Binds to 5-HT2C; Weakly inhibits norepinephrine reuptake
• Sertraline• Weakly inhibits norepinephrine and dopamine reuptake
• Paroxetine• Has significant anticholinergic activity at higher dosages
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Indications
• Depression• Anxiety Disorders• Obsessive-Compulsive Disorder• Panic Disorder• Social Anxiety Disorder• Post-Traumatic Stress Disorder• Generalized Anxiety Disorder
• Bulimia Nervosa• Off-label Uses: Premature ejaculation,
Paraphilias, Autism
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Side Effects
• Weight gain• Sexual Dysfunction: most common AE associated
with long-term treatment• Gastrointestinal: nausea, diarrhea, anorexia,
vomiting, flatulence, dyspepsia• Sertraline and Fluvoxamine produce the most
intense GI symptoms• Paroxetine, however, frequently produces
constipation.
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Side Effects
• CNS• Anxiety – seen during the first few weeks of
fluoxetine; seen less frequent with paroxetine and escitalopram• Insomnia – most commonly seen with Fluoxetine• Emotional Blunting• Yawning• Seizures – 0.1-0.2% incidence in SSRI treated
patients• Extrapyramidal symptoms
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Side Effects
• Hematologic: functional impairment of platelet aggregations easy bruising and excessive or prolonged bleeding• Endocrine: can acutely decrease glucose
concentrations• SEROTONIN SYNDROME: due to concurrent
administration of SSRI with a MAOI, L-tryptophan, or lithum
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Serotonin Syndrome• Signs arranged as condition worsens:• Diarrhea• Restlessness• Extreme agitation, hyperreflexia and autonomic instability
with possible rapid fluctuations in vital signs• Myoclonus, seizures, hyperthermia, uncontrollable shivering
and rigidity• Delirium, coma, status epilepticus, cardivascular collapse and
death• Treatment:• Remove offending agents • Nitroglycerine, cyproheptadine, methysergide (Samsert),
cooling blankets, Chlorpromazine, Dantrolene, benzodiazepines, anticonvulsants, mechanical ventilation, and paralyzing agents
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SELECTIVE SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRI)
Venlafaxine (Effexor)Duloxetine (Cymbalta)Desvenlafaxine (Pristiq)MilnacipranSibutramine (Meridia)
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Venlafaxine (Effexor)• Indications:• Depression, Generalized Anxiety Disorder, Social Anxiety
Disorder, Panic Disorder• May be beneficial in ADHD, OCD, Agoraphobia, and
Depression w/ Cocaine dependence• Adverse Effects:• Sweating is more common than with SSRIs• May cause MYDRIASIS – need to monitor patients with
narrow-angle glaucoma• Nausea, somnolence, dry mouth, dizziness, nervousness,
constipation, asthenia, anxiety, anorexia, blurred vision, abnormal ejaculation or orgasm, erectile disturbance, impotence
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Duloxetine• Indications: Depression,
GAD, Neuropathic pain associated with diabetes and stress urinary incontinence• Adverse Effects: • Nausea was the most
common side effect that lead to treatment discontinuation in clinical trials.
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SEROTONIN-NOREPINEPHRINE MODULATOR
Mirtazapine (Remeron)
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Mirtazapine (Remeron)• MOA:• Antagonism of central presynaptic α2-
adrenergic receptors causes increased firing of norepinephrine and serotonin neurons• Blockade of postsynaptic serotonin 5-
HT2 and 5-HT3 receptors • Indications• HIGHLY SEDATING and INCREASES
APPETITE makes it a reasonable choice for depressed patients melancholic features such as long-standing insomnia, weight loss and agitation
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NOREPINEPHRINE-DOPAMINE REUPTAKE INHIBITOR
Buproprion (Wellbutrin; Zyban)
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Bupropion (Wellbutrin)
• Does not act on the serotonin system little risk of sexual dysfunction or sedation and with modest weight loss during acute and long-term treatment• No withrawal syndrome linked to
discontinuation• Only medication approved by FDA for
prevention of seasonal depressive episodes of patients with seasonal affective disorder (SAD)• Brand name, Zyban, is also indicated for
smoking cessation
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Bupropion (Wellbutrin)
• Adverse Reactions:• Exerts indirect sympathomimetic
activity restlessness, agitation, irritability, positive inotropic effect on myocardium
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TRICYCLIC AND TETRACYCLIC ANTIDEPRESSANTS
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Tricyclics and Tetracyclics
• MOA: block the transporter site for norepinephrine and serotonin increase synaptic concentrations of these neurotransmitters• Indications same as SSRIs• How do they differ from SNRIs?• TCAs are nonselective since they also affect
muscarinic, adrenergic and histaminergic receptors MORE SIDE EFFECTS
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Tricyclics and Tetracyclics
• Each drug differs in its affinity for each transporter.• Clopipramine (Anafranil) – most serotonin
selective• Desipramine (Norpramin, Pertofane) – most
norepinephrine selective • Doxepin (Adapin, Sinequan) – most
antihistaminergic activity
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Tricyclics and Tetracyclics
• More likely to cause CONSTIPATION, sedation, dry mouth, or lightheadedness than the SSRIs• Less likely to cause sexual dysfunction, significant
long-term weight gain and sleep disturbances than the SSRIs.
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MONOAMINE OXIDASE INHIBITORS (MAOI)
Use limited to treatment-resistant cases due to risk of developing tyramine induced hypertensive crisis and consequent need for a restrictive diet.
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SEROTONIN MODULATORS
Trazodone (Desyrel)Nefazodone (Serzone)
Never achieved widespread use in treatment of MDD because they were too sedating at therapeutic doses.
Causes PRIAPISM in 1 of 10,000 men due to α1-adrenergic antagonism.
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B. PHARMACOTHERAPY FOR BIPOLAR DISORDER
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FDA-Approved Medications for Treatment of Bipolar Disorder
Agent Mania Maintenance
Aripiprazole (Abilify) Yes (2004) No
Carbamazepine XR (Equetro) Yes (2004) No
Divalproex (Depakote) Yes (1996) No
Lamotrigine (Lamictal) No Yes (2003)
Lithium (Lithobid) Yes (1970) Yes (1974)
Olanzapine (Zyprexa) Yes (2000) Yes (2004)
Risperidone (Risperdal) Yes (2003) No
Quetiapine (Seroquel) Yes (2004) No
Ziprasidone (Geodon) Yes (2004) No
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Lithium (Eskalith, Lithobid, Lithonate)
• Mechanism for mood-stabilizing effects of lithium still unknown• Indications:• Acute mania in Bipolar
Disorder• Augmentation of
antidepressants in MDD and antipsychotics in Schizoaffective and Schizophrenia Disorders
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Lithium (Eskalith, Lithobid, Lithonate)• Acute Manic Episodes in Bipolar
Disorder• Blood-brain-barrier permits
only slow passage of lithium onset of antimanic action can be slow (1-3 weeks)• supplemented in the early
phases of treatment by atypical antipsychotics, mood-stabilizing anticonvulsants, or high-potency benzodiazepines
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Lithium (Eskalith, Lithobid, Lithonate)• Maintenance treatment with Lithium• markedly decreases the frequency, the severity, and the
duration of manic and depressive episodes in persons with bipolar I disorder
• provides relatively more effective prophylaxis for mania than for depression
• indicated after the second episode of bipolar I disorder depression or mania and should be considered after the first episode for adolescents or for persons who have a family history of bipolar I disorder
• reduces the incidence of suicide in patients with bipolar I disorder sixfold or sevenfold.
• Lithium is also effective treatment for persons with severe cyclothymic disorder.
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Lithium ToxicityMild to Moderate Toxicity (lithium level = 1.5 to 2.0 mEq/L)
Gastrointestinal Vomiting, Abdominal pain, Dryness of mouth
Neurologic Ataxia, Dizziness, Slurred speech, Nystagmus, Lethargy or excitement, Muscle weakness
Moderate to severe intoxication (lithium level = 2.0 to 2.5 mEq/L)
GI Anorexia, Persistent nausea and vomiting
Neurologic Blurred vision, Muscle fasciculations, Clonic limb movementsHyperactive deep tendon reflexes, Choreoathetoid movementsConvulsions, Delirium, Syncope, Electroencephalographic changes, Stupor, Coma, Circulatory failure (lowered BP, cardiac arrhythmias, and conduction abnormalities)
Severe lithium intoxication (lithium level >2.5 mEq/L)
Generalized convulsions Oliguria and renal failure Death
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Lamotrigine (Lamictal)
• antiepileptic drug used as adjunctive therapy for general and partial seizures in adults and pediatric patients• shown to keep patients euthymic longer and was
particularly effective in preventing depressive episodes• no significant metabolic or neurologic effects,
and does not require laboratory testing of plasma concentrations BUT has no acute antimanic effects
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Lamotrigine (Lamictal)
• MOA: • blockade of voltage-sensitive sodium channels modulate release of glutamate and aspartate, and slight effect on calcium channels. • Modestly increases plasma serotonin
concentrations, possibly through inhibition of serotonin reuptake, and is a weak inhibitor of serotonin 5-HT3 receptors.
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Lamotrigine
• most common adverse effects are mild: dizziness, ataxia, somnolence, headache, diplopia, blurred vision, nausea, joint or back pain• Important AE: RASH which is common and
occasionally very severe. • 8% of patients develop a benign
maculopapular rash during the first 4 months of treatment• drug should be discontinued if a rash develops
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Carbamazepine• first used to treat partial- and generalized-onset epilepsy and
trigeminal neuralgia• been used for decades as a first-line agent for acute and maintenance
treatment for bipolar I disorder OUTSIDE THE UNITED STATES• Anticonvulsant MOA: • Prolongs inactive state of voltage-dependent sodium channels
reduces voltage-dependent calcium channel activation and, therefore, synaptic transmission
• reduction of currents through N-methyl-D-aspartate (NMDA) glutamate-receptor channels
• competitive antagonism of adenosine A1 receptors• potentiation of central nervous system (CNS) catecholamine
neurotransmission.• MOOD STABILIZING MOA UNKNOWN
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Valproate, Divalproex
• MOA poorly understood.• Postulated mechanisms include• enhancement of γ-aminobutyric acid
(GABA) activity, modulation of voltage-sensitive sodium channels, and action on extrahypothalamic neuropeptides.• Antimanic response elicited at higher
therapeutic
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Valproate, Divalproex• Psychiatric Indications:• Schizophrenia and Schizoaffective Disorder• Valproate may accelerate response to antipsychotics• Valproate alone is ineffective for treatment of psychotic symptoms
• Bipolar I Disorder• Acute Mania• 2/3 of patients with mania usually respond within 1 to 4 days
after achieving valproate serum concentrations above 50 µg/mL. short-term antimanic effects of valproate can be augmented with addition of lithium (Eskalith), carbamazepine (Tegretol), or dopamine receptor antagonists (DRAs).
• Mixed Episodes• Acute Bipolar Depression• effect is far less pronounced than for treatment of manic
episodes. • Among depressive symptoms, valproate is more effective for
treatment of agitation than dysphoria.
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IV. ANXIETY DISORDERS
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A. SEDATIVE-HYPNOTICS
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• Sedative (anxiolytic) agent - reduces anxiety and exerts a calming effect. The degree of central nervous system depression caused by a sedative should be the minimum consistent with therapeutic efficacy.• Hypnotic drug - produce drowsiness and
encourage the onset and maintenance of a state of sleep• involve more pronounced depression of the
central nervous system than sedation
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Subclasses
• Benzodiazepines• Barbiturates• Newer Hypnotics• Melatonin receptor agonist• 5-HT-receptor agonist
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Benzodiazepines
• Mechanism of action• enhance GABA's effects
allosterically without directly activating GABAA receptors or opening the associated chloride channels• Increases frequency of
channel-opening events enhancement in chloride ion conductance
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BenzodiazepinesQuickest onset of action Shortest-acting (plasma
half lives of < 30 hours)Longest-acting (plasma half lives of 30 to > 100 hours)
Diazepam (Valium) Oxazepam (Serax) Diazepam
Lorazepam (Ativan) Terazepam (Restoril) Chlordiazepoxide
Alprazolam (Xanax) Estazolam Clonazepam (Klonopin)
Triazolam (Halcion) Alprazolam Clorazepate
Estazolam (Prosom) Triazolam – shortest half-life (2-3 hours)
Flurazepam (Dalmane) – longest half-lifePrazepam (Centrax)
Quazepam (Doral)
Halazepam (Paxipam)
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Psychiatric Indications of Benzodiazepines• Insomnia• Flurazepam – minor cognitive impairment on
the day after its administration• Triazolam – mild rebound anxiety and
anterograde amnesia• Quazepam – daytime impairment when used
for a long time• Temazolam• Estazolam – rapid onset of sleep and a
hypnotic effecto for 6-8 hours
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Psychiatric Indications of Benzodiazepines• Generalized Anxiety Disorder• Panic Disorder – Alprazolam and clonazepam used in
conjunction with SSRIs tapered after 3-4 weeks when benefits of SSRIs emerge• Social Phobia – clonazepam• PTSD and OCD• Anxiety with Depression – alprazolam• Bipolar I disorder – clonazepam, lorazepam and
alprazolam• Alcohol Withdrawal – chlordiazepoxide (Librium)• Substance-Induced or Psychotic-Induced Agitation
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Adverse Effects of Benzodiazepenes
• Most common: DROWSINESS, residual daytime sedation• Ataxia (< 2%)• Dizziness (< 1%)• Teratogenic• Impairment of respiration in patients with COPD
and sleep apnea• Alprazolam can can exert a direct appetite
stimulant effect and cause weight gain.
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Newer hypnotics - Zolpidem, Zaleplon, Eszocpiclone• Indicated for insomnia• Zolpidem 10 mg QID may be used in
Parkinson’s Disease• Mechanism of action: • Selective binding of certain units of GABAA
receptor selective sedative effects and relative lack of muscle relaxant and anticonvulsive effects
• Adverse Effects:• Zolpidem – Anterograde amnesia, Dizziness,
drowsiness, dyspepsia, or diarrhea, hallucinations and behavioral changes• Eszopiclone in elderly patients - Pain, dry
mouth and unpleasant taste
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Barbiturates
• High abuse and addiction potential• narrow therapeutic range with low therapeutic
index and unfavorable side effects • Indications:• Methohexital (Brevital) – anesthetic agent for
ECT (0.7-1.2 mg/kg) and can be used to abort prolonged seizures in ECT or to limit post-ictal agitation; brief duration of action: 5-7 minutes• Phenobarbital (Solfoton, Luminal) – for
generalized tonic-clonic and simple partial seizures; 10-20 mg/kg IV for status epilepticus
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Barbiturates• Mechanism of action:• increase the duration of the GABA-
gated chloride channel openings high chloride-ion conductance
• barbiturates may also be GABA-mimetic binding to sites different than those of benzodiazepines directly activating chloride channels
• Barbiturares can depress the actions of the excitatory neurotransmitter glutamic acid via binding to the AMPA receptor.
• nonsynaptic membrane effects in parallel with their effects on GABA and glutamate
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Buspirone
• Demonstrated efficacy only in the treatment of GAD• Mechanism of action: UNCLEAR – proposed
mechanisms are presynaptic and postsynaptic 5-HT1A agonist with some effect on D2 receptors• Adverse effects:• Headache, nausea, dizziness, and rarely insomnia• No weight gain, sexual dysfunction, sleep
disturbance, or discontinuation syndrome• No sedation or cognitive and psychomotor
impairment
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Ramelteon (Rozerem)
• For the treatment of INSOMNIA characterized by difficulty with sleep onset• Mechanism of Action: targets the melatonin MT1
and MT2 receptors in the suprachiasmatic nucleus (SCN)• Dosage: 8 mg within 30 minutes before going to
bed• Adverse Events: somnolence, dizziness, and
fatigue
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References:
• American Psychiatric Association. 2010. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd ed• Katzung BG, Masters SB, Trevor AJ. 2009. Basic &
Clinical Pharmacology, 11th Edition. McGraw-Hill• Sadock BJ and Sadock VA. 2007. Kaplan &
Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition. Lippincott Williams & Wilkins