Antidepressants Flashcards
Factors favoring treatment with an antidepressant: (response can be expected in 50-75% of pts.)
- Agitation
- Problems with sleep and/or appetite
- history of response to antidepressant, patient preference and moderate to severe symptoms.
Choice of Antidepressant
- Antidepressant response history (if not initial episode)
- Comorbidities
- Depressive symptoms
- Safety/tolerability (MAOIs and TCA’s are not appropriate first-line agents due to side effects and food, drug interactions with MAOIs)
- Drug interactions
- Pharmacokinetics
- Cost
- Patient preference
For most patients, the initial therapy will be with
a SSRI, SNRI, bupropion (Wellbutrin) if no anxiety component of depression, a dopamine-reuptake inhibitor or mirtazapine (Remeron) an alpha-2 antagonist
Depression with pain consider
SNRI orTCA
Depression w nicotine addiction
Bupropion (Wellbutrin)
Depression with loss of appetite, weight loss and/or insomnia
Mirtazapine (Remeron)
Mirtazapine (Remeron)
Increases appetite
Somnolence may be an issue at lower doses but not at higher doses
SSRIs from most energizing (activating) to the most sedating
Fluoxetine (Prozac),
Sertraline (Zoloft),
Citalopram (Celexa),
Escitalopram (Lexapro),
Paroxetine (Paxil).
When treating depression w/ anxiety:
- Use a less energizing SSRI, Venlafaxine or Duloxetine.
- Consider Viibryd if others fail.
- If you use Fluoxetine in a patient w/ anxiety be sure to start low and titrate slowly to avoid activation of anxiety
- Avoid Wellbutrin as this is too activating and can cause increased anxiety.
Most common clinical mistake leading to an unsuccessful trial of an antidepressant drug is
the use of too low a dosage for too short a time. Unless adverse events prevent it, the dosage of an antidepressant should be raised to the maximum recommended level and maintained at that level for at least 4 or 5 weeks before a drug trial is considered unsuccessful
Side Effects (in general)
- Take advantage of the side effects of a medication such as utilizing utilize a sedating antidepressant in a patient with insomnia.
- For undesirable side effects, the provider can lower the dose or switch to an agent with a different side effect profile.
To reduce side effects of Sexual Dysfunction
- For a reduction in sexual side effects which are common with SSRIs, SNRIs, and TCAs, bupropion is recommended.
- If the antidepressant is working well and you do not want to switch to bupropion, this can be added to an SSRI. - Other add-ons include buspirone or a phosphodiesterase inhibitor.
- Sildenafil does reduce and tadalafil may reduce SSRI-induced sexual dysfunction in men, whereas bupropion may be effective in both men and women.
GI Side Effects
Nausea and vomiting are not uncommon with SSRIs and SNRIs; especially fluoxetine (Prozac), venlafaxine(Effexor) and duloxetine (Cymbalta). These side effects typically decrease with continued treatment. Diarrhea may be a persistent problem with sertraline (Zoloft). To decrease nausea have the patient take the medication with food or divide doses.
Activation, agitation, restlessness, insomnia and anxiety may occur with
SSRIs, SNRIs and buproprion. These side effects may be reduced over time.
can cause akathisia (inner restlessness)
SSRIs and SNRIs
Insomnia may be reduced through
a.m. dosing, good sleep hygiene, CBT, melatonin or adding trazodone, a serotonin reuptake inhibitor/antagonist.
Sedation is most common with
TCA’s, mirtazapine at low doses and nefazodone. Paroxetine (Paxil) tends to be the most sedating of the SSRIs and is a good choice for a patient with depression and overlying anxiety.
a good choice for patients with fatigue or sleepiness
Buproprion
Diarrhea may be a persistent problem with
sertraline (Zoloft).
Nausea and vomiting are not uncommon with
SSRIs and SNRIs; especially fluoxetine (Prozac), venlafaxine(Effexor), and duloxetine (Cymbalta)
Reduces sexual dysfunction in men
Sildenafil does reduce and tadalafil may reduce SSRI-induced and bupropion may be effective
Reduces sexual dysfunction in women
bupropion may be effective
Weight Gain
- The most common SSRI to cause weight gain is paroxetine (Paxil)
- TCAs often cause weight gain
Are weight neutral or may cause a modest weight loss.
Bupropion (Wellbutrin) and fluoxetine (Prozac)
May cause weight loss
Venlafaxine (Effexor)
Discontinuation Syndrome if not Tapered
- Paroxetine (Paxil) is the most common SSRI with venlafaxine (Effexor) being the next most likely to cause this syndrome with abrupt discontinuation.
- Fluoxetine (Prozac) is least likely.
S/Sx of Discontinuation Syndrome
typically flu-like or neurologic.
For patients with compliance issues
an SSRI such as Fluoxetine (Prozac) is likely a good choice to avoid recurrent discontinuation syndrome symptoms.
Anticholinergic Side Effects
- TCAs can cause anticholinergic symptoms of mental status changes, urinary retention, and blurred vision.
- Desipramine has the least anticholinergic side effects
- Amitriptyline has the greatest anticholinergic side effects of TCAs.
- SNRIs and bupropion can also cause dry mouth and constipation.
Arrhythmias and Orthostatic Hypotension
TCAs have the potential to cause arrhythmias which are lethal with an overdose. This is why, with a potentially suicidal patient, providing a script for TCAs would be contraindicated.
If starting a patient over 50 on a TCA
an ECG should be done as well as a cardiovascular risk assessment.
FDA recommends against using doses > 40 mg/day of Citalopram (Celexa)
due to the possible increased risk of QT interval prolongation and torsade de pointe.
Citalopram (Celexa) is associated with
potentially fatal abnormal heart rhythms such as QT interval prolongation and torsade de pointe.
dose-dependent HTN caused by
buproprion (Wellbutrin),
venlafaxine (Effexor),
duloxetine (Cymbalta),
desvenlafaxine (Pristiq)
hypertensive crisis may be caused by
MAOs combined with SSRIs, SNRIs, and TCAs
Serotonin Syndrome is more commonly seen with
an SSRI is combined with another drug such as a triptan, tramadol, or linezolid
Serotonin Syndrome is most severe when
an SSRI is combined with an MAOI
Which SSRIs are the most significant enzyme inhibitors are
fluoxetine (Prozac), fluvoxamine (Luvox) and paroxetine (Paxil)
the greatest potential for inhibition of the metabolism of other drugs among the SNRIs
Duloxetine (Cymbalta)
Initial improvement
may be seen in 1 to 2 weeks but typically the maximum improvement ranges from four to 12 weeks are required.
If no response is seen in 4 to 8 weeks with the maximally tolerated dose
then options are to switch to a different antidepressant within the same or different class.
After complete remission of symptoms, antidepressant therapy should continue for
at least four to nine months (you may see up to 12 months in the literature as well).
who will most likely need continuous maintenance therapy
Individuals who have had three or more episodes of depression most likely will need continuous maintenance therapy. You may see two or more episodes in some of the literature as well.
A response is characterized as at least
a 50% improvement in symptoms.
When treatment of depression results in the removal of essentially all symptoms,
is called remission for the first several months (e.g., up to 6 months).
Recovery is described as
being symptom-free for 6 months or more.
a relapse is
When depression returns before there is a full remission of symptoms or within the first several months following remission of symptoms,
When depression symptoms return after a patient has recovered
it is called a recurrence
SIGECAPS
Sleep disturbances
Interest decreased in pleasure activities and sex
Guilty feelings
Energy decreased
Concentration decreased
Appetite (up or down)
Psychomotor function decreased
Suicidal ideations
Specifiers for depressive disorders
Anxious
Mixed features (see bipolar)
Melancholic
with Psychosis
Catatonic
Peripartum/postpartum
Seasonal
Atypical
The objective of pharmacologic treatment is
symptom remission, not just symptom reduction.
PHARMACOTHERAPY of antidepressants
- The use of pharmacotherapy approx. doubles the chances that a depressed patient will recover in 1 mos.
- Efficacy is similar across all antidepressants, Tolerability will vary
- All current anti-depressants may take up to 3 to 4 weeks to exert significant effects earlier
- Choice of antidepressants is determined by the side effect profile related patient’s physical status, temperament, and lifestyle.
- Continued symptoms without full remission—likely to cause relapse or reoccurrence of depressive episodes & impaired functioning
CLINICAL GUIDELINES
- The most common clinical mistake leading to an unsuccessful trial of an antidepressant drug is the use of too low a dosage for too short a time*
- Unless adverse effects prevent it, the dosage of an antidepressant should be raised to the maximum recommended level and maintained at that level for at least 4 or 5 weeks before a drug trial is considered unsuccessful.
- Alternatively, if a patient is improving clinically on a low dosage of the drug, the dosage should not be raised unless clinical improvement stops before maximal benefit
obtained. - If not responding to appropriate dosages within 2-3 weeks, clinicians can decide whether to test plasma concentrations or rule out noncompliance or unusual
pharmacokinetic response - Assess pharmacokinetics to assess which meds may require a higher or lower dose based on metabolism
INITIAL MEDICATION SELECTION
- No difference in overall efficacy, speed of response, or long-term effectiveness
- Differ in pharmacology, drug-drug interactions, short/long term SE’s, discontinuation symptoms, ease of dose adjustment
- Start with Selective serotonin reuptake inhibitors (SSRIs)- most commonly prescribed for depression
- Depends on family history & treatment response, course of illness, chronic illness, symptoms severity, concurrent medical conditions
- Drug-drug interactions, and patient preference. Earlier
treatment response predicts future responses
DURATION
Antidepressant treatment should be maintained for at least 6 mos. or the length of a previous episode, whichever is greater.
drug dose should be tapered gradually over
1 to 2 weeks, depending on the half-life of the drug
MDD with psychosis may require a combo:
antidepressant+ atypical antipsychotic
ACUTE TREATMENT FAILURES
- Inability to tolerate side effects even with a positive response to treatment
- Development of an adverse side effect
- Lack of response from treatment
- Incorrect diagnosis
TYPES OF ANTIDEPRESSANTS
SSRIs
Fluoxetine, Sertraline, Citalopram, Escitalopram, Paroxetine, Fluvoxamine
SNRIs
Venlafaxine, Duloxetine, Desvenlafaxine, levomilnacipran
TCAs
Amitriptyline, Nortriptyline, Imipramine, Doxepin, Desipramine
Atypicals
(Tetracyclic: Mirtazapine & Trazodone)
Bupropion (NDRI), Mirtazapine, Trazodone
MAOIs
Nardil, Parnate, Marplan
SPARI (SSRI and Serotonin Modulators)
Vilazodone, Votioxetine
SEROTONIN SYNDROME - Cause:
Taking more than one serotonin-related medication
(prescription & CAM) - St. John’s Wart, SAMe, concurrent MAOI, Lithium
SEROTONIN SYNDROME - Symptoms
PROGRESSION
1. diarrhea & cramps,
2. restlessness,
3. extreme agitation;
hyperreflexia (overactive or overresponsive reflexes);
autonomic instability (rapid fluctuations in vitals)
4. Myoclonus (sudden, involuntary jerking of a muscle or group of muscles), Seizures, Hyperthermia, shivering (uncontrollable), rigidity:
5.Delirium, coma, status epilepticus, CV collapse,
Death
Other: Diaphoresis, Tremor, Chills,, Ataxia (loss of full control of bodily movements), Headache, Insomnia
SEROTONIN SYNDROME - Treatment
DC SSRI;
Muscle Relaxants (Dantrium);
Serotonin Blocking Agents (Periactin-);
O2; IV fluids; Meds to control BP and HR;
A breathing tube and medication to paralyze your muscles
