PSYCHOPHARMACOLOGY: ANTIDEPRESSANTS

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PSYCHOPHARMACOLOGY ANTIDEPRESSANTS

• Lloyda B. Williamson, M.D., Assist. Prof.
• Dept. of Psychiatry Behavioral Medicine
• University of Alabama,School of Medicine,
• Tuscaloosa Campus
• April 3, 2007

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General Principals of Psychopharmacology

• When selecting a medication
• consider the diagnosis identify target
  symptoms tailor your choice of drug to the side
  effects that may be helpful or avoid ones that
  may be harmful Eg. Sedation, weight gain
• note drugs currently taken as well as those
  recently discontinued (include review of
  over-the counter medications and herbal
  preparations) Eg. If a seizure disorder, do not
  use Wellbutrin

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General Principles of Psychopharmacology -cont.

• if a low dose is currently being taken of a drug,
  continue the drug at a higher dosage to complete
  a therapeutic trial push dose to maximum dosage
  until patient experiences medication side effects
  or improves do this BEFORE switching or adding
  another medication also causes less confusion in
  the future Eg. Zoloft 75mg daily is not maximum

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General Principles of Psychopharmacology -cont.

• review all all of the patients problems
  resources (eg. Insurance)
• consider patient/ family history of drug response
  Eg. Positive response runs in families
• obtain medical records if the patient is unsure
  of previous unsuccessful/ successful drug trials
  Eg. Avoid repeating bad experiences
• consider co-morbid conditions Eg. Diabetes,
  obesity, hypertension

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General Principles of Psychopharmacology -cont.

• note risk of suicide Eg. Avoid tricyclic
• consider patient preference, Eg. positive or
  negative experience can influence their response
• start ONE medication at a time, so that if
  adverse effects occur it will be clearer as to
  which medication was the cause
• titrate dosages of ONE medication at a time
• start with low doses to minimize side effects

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General Principles of Psychopharmacology -cont.

• allow adequate time for the drug to reach its
  therapeutic effect before considering a dose
  increase Eg. Changing Prozac dose every 2 -3
  weeks will not help you determine accurate
  response
• check patient understanding compliance
  throughout drug trial, Eg. Taking daily instead
  of only when they feel bad? Obtain refills?
  Taking as prescribed, BID or TID?

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General Principles of Psychopharmacology -cont.

• Note children geriatric patients may require
  lower dosages that typical adult dosages eg.
  Elderly patients may have decreased liver
  function, resulting in decreased Phase I
  metabolism by cytochrome P450 enzymes may
  otherwise choose medication metabolized by Phase
  II reactions such as glucuronidation

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General Principles of Psychopharmacology -cont.

• Af-Am more likely than European descent to be
  slow metabolizers of antidepressants due to
  genetic differences in metabolic enzyme
  expression thus Af-Am may have higher plasma
  levels per dose of antidepressant (noted with
  TCAs)
• Asians are slower to metabolize some TCAs than
  other groups
• choose the form of medication most appropriate
  for the patients lifestyle eg. Extended release
  formulations

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General Principles ofPsychopharmacology cont.

• Women- slower GI absorption than men due to less
  gastric acid slower gastric emptying
• Women- different volume of distribution with
  increased ratio of adipose tissue to lean body
  mass water retention may also affect volume of
  distribution
• Oral contraceptives may alter metabolism of TCAs

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General Principles ofPsychopharmacology cont.

• Discuss medications with women regarding
  potential pregnancy BEFORE pregnancy
• consider the benefits verses the risks of
  continuing medication during pregnancy usually
  it is best to continue the medication during
  pregnancy

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Antidepressants

• Are considered equally effective in treating
  depression
• Differ in safely and side effect profiles
• 70 of patients with Major Depression will
  respond to antidepressant medication
• Have no abuse potential

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Antidepressants

• They are not
• just for depression
• anymore!

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Antidepressants areused to treat

• Autism (SSRIs)
• Dysthymia (SSRIs)
• Eating Disorders (SSRIs, TCAs, MAOIs)
• Enuresis (TCAs)
• Irritable Bowel Syndrome (SSRIs,TCAs)
• Migraine Headaches (TCAs, SSRIs, Buproprion)
• Neuropathic pain analgesic (TCAs)

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Antidepressant areused to treat (cont.)

• Obsessive-compusive Disorder (SSRIs, TCAs)
• Panic Disorder (SSRIs,TCAs, MAOIs)
• Posttraumatic Stress Disorder (SSRIs, TCAs)
• Premenstrual Dysphoric Disorder (SSRIs)
• Smoking Cessation (Buproprion)

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1)Tricyclic Antidepressants

• Mechanism of action block the reuptake of
  norepinephrine and serotonin, increasing the
  availability in the synapse
• Rarely used as first-line agents because they
  have a higher incidence of side effects, require
  closer monitoring of dosing and can be lethal in
  overdose

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1)Tricyclic AntidepressantSide Effects

• Antiadrenergic effects orthostatic hypotension,
  tachycardia, arrythimias
• Antihistaminic effects sedation
• Antimuscarenic effects dry mouth, constipation,
  urinary retention, blurred vision, tachycardia
• Weight gain
• Other complications convulsions, coma,
  cardiotoxicity

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1)Tricyclic AntidepressantsDrug Interactions

• Use with Lithium may increase neurotoxicity
• SSRIs inhibit metabolism of TCAs may lead to
  toxicity

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1)Tricyclic Antidepressant Medications

• Amitriptyline (Elavil)
• Clomipramine (Anafranil) most serotonin specific
• Desipramine (Norpramine) least sedating, least
  anticholinergic side effects
• Doxepin (Sinequan)
• Imipramine (Tofranil)
• Nortriptyline (Pamelor)
• Protriptyline (Vivactil)
• Trimipramine (Surmontil)

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1)Tricyclic Antidepressant Medications

• (continued)
• Related Tricyclics
• Maprotiline (Ludiomil) a tetracyclic
• Amoxapine (Ascendin) a dibenzoxapine

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2)Monoamine Oxidase Inhibitors (MAOIs)

• Mechanism of action block the activity of
  monamine oxidase, resulting in decrease of the
  breakdown of dopamine, serotonin norepinephrine
  in synapse

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2)Monoamine Oxidase Inhibitors (MAOIs)

• -MAOIs are not used as first-line agents because
  of increased safety and tolerability of newer
  agents. However, they are considered very
  effective fore certain types of refractory
  depression and in refractory panic disorder

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2)Monoamine OxidaseInhibitor Side Effects

• Common side effects headache, insomnia,
  diarrhea, dry mouth, orthostatic hypotension,
  drowsiness, weight gain, sexual dysfunction, dry
  mouth, sleep dysfunction, rash, dyspepsia

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2)Monoamine Oxidase Inhibitor Side Effects (cont)

• Hypertensive crisis occurs when MAOIs are taken
  with tyramine-rich foods or sympathomimetics (as
  found in over-the-counter cold remedies, diet
  pills, amphetamines)
• Foods rich in tyramine aged cheese, yogurt,
  Chianti wine, foreign beer, liver, snails,
  pickled herring, chocolate, broad beans, soy
  sauce, avocados

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2)Monoamine Oxidase Inhibitor Drug Interactions

• Serotonin syndrome occurs when SSRIs and MAOIs
  are taken together lethargy, restlessness,
  confusion, flushing, diaphoresis, tremor, and
  myoclonic jerks may progress to hyperthermia,
  hypertonicity, rhabdomyolysis, renal failure,
  convulsions, coma and death wait 2 weeks before
  switching from SSRI to MAOI

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2)Monoamine Oxidase Inhibitor Medications

• Phenelzine (Nardil)
• Tryaylcypromine (Parnate)
• Isoparboxazide (Marplan)
• Emsam (Selegiline transdermal)
• -no dietary restrictions at 6 mg dose

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3)Selective Serotonin Reuptake Inhibitors (SSRIs)

• Mechanism of action block presynaptic serotonin
  pumps, resulting in increased availability of
  serotonin in synaptic clefts
• All have similar efficacy and side effects
  despite structural differences
• Differ in their half-life, potency for reuptake
  inhibition affinity for other receptors

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3) SSRIs (cont.)

• Advantages of their use include the following
  low incidence of side effects compared to other
  agents, safer in cases of overdose, no food
  restrictions

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3) SSRISide Effects

• Anorexia, weight loss or weight gain
• Gastrointestinal disturbance, nausea
• Headache
• Insomnia or sedation
• Serotonin syndrome when used with MAOIs
• Sexual dysfunction

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3) SSRI Medications

• Citalopram (Celexa)
• -related, but NOT the generic form of Lexapro
• Celexa Lexapro ratio is about 41
• Fluoxetine (Prozac)- longest half-life
• Fluvoxamine (Luvox)
• Paroxitine (Paxil)- shortest half-life
• Sertraline (Zoloft)- higher rate of GI side
  effects
• Escitalopram (Lexapro)-most serotonin specific

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4) 2nd Generation Antidepressants

• Norepinephrine/ dopamine reuptake inhibitor
  (NDRI), primarily dopaminergic effect
• -Buproprion (Wellbutrin) useful in Major
  Depression, smoking cessation, and in Attention
  Deficit Hyperactivity Disorder lack of sexual
  side effects as compared to the SSRIs low drug
  interaction potential
• -Side effects increased sweating and increased
  risk of seizures and psychosis at doses above 450
  mg

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5) 3rd Generation Antidepressants

• A)Serotonin/norepinephrine reuptake inhibitors
  (SNRIs)
• -Venlafaxine (Effexor) has low drug interaction
  potential side effects include headache,
  dizziness, insomnia, nervousness, nausea also
  used with pain
• -Duloxatine (Cymbalta) especially useful in
  treating depression associated with pain side
  effects include nausea and fatigue

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3rd Generation Antidepressants (cont.)

• B) Serotonin agonist reuptake inhibitors
  (SARIs)
• -Nephazodone (Serzone) no longer available
• -Trazodone (Desyrel) useful in treating
  depression with insomnia side effects include
  nausea, dizziness, hypotension, sedation, and
  priapism (persistant abnormal erection of penis
  treat with intracorporeal epinephrine)

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3rd GenerationAntidepressants (cont.)

• Mixed serotonin antagonist/ noradrenaline
  angatonist
• -mirtazepine (Remeron)
• -blocks receptors of the alpha-2-autoreceptors
  on presynaptic noradrenergic neurons, which
  enhances noradrenergic output may also do the
  same towards serotonin autoreceptors