Chapter 15 Psychopharmacology for Pain Medicine Flashcards
A large percentage of patients with chronic pain disorders have coexisting or comorbid
Psychiatric Conditions
Psychotherapeutic modalities
Cognitive Behavioral Therapy, Relaxation training, or Biofeedback
The majority of patients with psychiatric comorbidity developed their psychiatric illness
after the onset of chronic pain
Type of psychiatric illness
Major depression alone affects 30% to 50% of all pain clinic patients, followed by anxiety disorders, personality disorders, somatoform disorders, and substance use disorders.
Most frequently affect patients with chronic pain
Major Depression and Anxiety disorders are the most common and have the best response to medications
According to the DSM-IV, major depressive disorder (MDD) requires two key features
depressed mood and loss of interest or pleasure in most activities (anhedonia) for at least 2 weeks
Major depression can be distinguished from situational depression (also termed “demoralization” or an “adjustment disorder with depressed mood”) by
the triad of persistently low mood, self-attitude changes, and changes in vital sense, all lasting at least 2 weeks. Low mood manifests itself by emotions of “feeling blue,”
down, or depressed.
Anhedonia
the inability to experience pleasure, is a key reflection of low mood
A diminished self-attitude is seen in
thoughts of guilt or thinking that one is a bad person
Changes in vital sense
refer to changes in sleep, appetite, or energy levels.
Depressive symptoms
may present as Beck’s triad, with patients feeling hopeless, hapless, and helpless. They
see the future as bleak, they feel they cannot help themselves, and no one can help them
Suicidal thoughts reflect
the severity of depressive symptoms.
Antidepressants can take up to how long for an initial response and for full clinical improvement?
Antidepressants can take up to 2 to 4 weeks for an initial response, but all can take 4 to 8 weeks for full clinical improvement after a typical dose is reached
For depressed patients who also suffer from comorbid pain should remain on them for how long?
For 6 to 12 months for the treatment of an initial depressive episode, and 5 years for the treatment of a recurrent depressive episode
What group of patients tend to respond at lower doses of antidepressants?
Older adults tend to respond at lower doses of antidepressants, and dose titration should occur more slowly in this group because of
their heightened sensitivity to side effects and toxicity.
Good rule of thumb in starting antidepressants in any age
group
is to begin with 25% to 50% of the standard initial
treatment dose for a week, and then advance gradually
over the next 2 to 3 weeks to the treatment dose. This
minimizes side effects and increases treatment compliance
What drug should not be prescribed with other antidepressants?
Monoamine oxidase inhibitors (MAOIs), such as phenelzine, which are rarely prescribed anymore, should not be prescribed with other antidepressants concurrently
The most efficacious treatment for major depression?
Cognitive behavioral therapy (CBT) in conjunction with
antidepressant therapy
- SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI’s)
Fluvoxamine (Luvox) Fluoxetine (Prozac) Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro) Venlafaxine (Effexor)
SSRI Mechanism of Action
They have an immediate effect on the blockade of the presynaptic serotonin reuptake pump in the central nervous system (CNS), to increase the duration of serotonin in the synaptic cleft, increasing the effects of
neurotransmission
Adverse effect that all SSRIs have been associated with
Easy bruising/bleeding and osteoporosis
SSRIs can lead to serotonin syndrome when given with other medications including
SNRIs, TCA, MAOIs, triptans (e.g., sumatriptan), and antiemetics (e.g., ondansetron, metoclopramide).
- A serotonin syndrome can be precipitated by a combination of SSRIs and multiple analgesics, including
Tramadol, meperidine, fentanyl, and pentazocine
The use of SSRIs in combination with tramadol can
Lower the seizure threshold, and caution should be taken if combining these drugs
Fluoxetine (Prozac) and Paroxetine effects
Fluoxetine tends to be more activating and is prescribed in the morning, while paroxetine with its anticholinergic effect of activating muscarinic receptors, is more sedating and has greater anxiolytic properties
Sertraline and citalopram
Tend to be less sedating than paroxetine and are generally prescribed to be taken in the morning
Side Effects of SSRI
Patients should begin on one-half of the usual dose for
a week and then to the standard dose, to minimize the side effects of nausea, diarrhea, tremor, and headache
Approximately 75% to 80% of patients on SSRIs can experience sexual side effects, such as
Decreased libido, impotence, ejaculatory disturbances, or
anorgasmia.
Rare side effects of SSRI include
Dystonia, Akathisia, Palpitations, A lowered seizure threshold, Serotonin Syndrome, or syndrome of inappropriate antidiuretic hormone (SIADH).
Dystonia: a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.
Akathisia: is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless.
Metabolism of SSRI
SSRIs are metabolized by hepatic oxidation, and their use
may alter the serum levels of other hepatically metabolized drugs.
SSRIs induce and/or inhibit various cytochrome P450 enzymes. Drugs effected are
Most significantly, they can increase levels of tricyclic antidepressants and benzodiazepines. They may
also affect levels of carbamazepine, lithium, antipsychotics, and commonly used analgesics, such as methadone, oxycodone, and fentanyl.
In discontinuing SSRIs, they should be
Tapered down slowly to avoid a withdrawal syndrome, which has the same symptoms as initiation of SSRIs (headache, nausea, diarrhea, or myalgias)
Selective Serotonin Reuptake Inhibitors (SSRIs) and Usual Start Dose
Citalopram (Celexa) 10 mg qd Fluoxetine (Prozac) 10 mg qd Fluvoxamine (Luvox) 25 mg qd Paroxetine (Paxil) 5-10 mg qd Sertraline (Zoloft) 25 mg qd
Selective Serotonin Reuptake Inhibitors (SSRIs) and Average Dose
Citalopram (Celexa) 20–40 mg qd Fluoxetine (Prozac) 20–40 mg qd Fluvoxamine (Luvox) 50–100 mg bid Paroxetine (Paxil) 20–40 mg qd Sertraline (Zoloft) 50–150 mg qd
Selective Serotonin Reuptake Inhibitors (SSRIs) and Maxiumum Dose
Citalopram (Celexa) 60mg/d Fluoxetine (Prozac) 80mg/d Fluvoxamine (Luvox) 300mg/d Paroxetine (Paxil) 60mg/d Sertraline (Zoloft) 200 mg /d
- TRICYCLIC ANTIDEPRESSANTS (TCAs)
Amitriptyline (Elavil) Amoxapine (Asendin) Clomipramine (Anafranil) Desipramine (Norpramin) Doxepin (Sinequan) Nortriptyline (Pamelor) Protriptyline (Vivactil)
TRICYCLIC ANTIDEPRESSANTS (TCAs) Usual Start Dose
Amitriptyline (Elavil)10- 25 mg qd Amoxapine (Asendin)25 mg bid Clomipramine (Anafranil)25 mg qd Desipramine (Norpramin)10- 25 mg qd Doxepin (Sinequan)10- 25 mg qd Nortriptyline (Pamelor) 10- 25 mg qd Protriptyline (Vivactil) 5 mg qd
TRICYCLIC ANTIDEPRESSANTS (TCAs) Average Dose
Amitriptyline (Elavil) 75–150 mg qd Amoxapine (Asendin) 75–200 mg bid Clomipramine (Anafranil) 150–250 mg qd Desipramine (Norpramin) 75–150 mg qd Doxepin (Sinequan) 75–150 mg qd Nortriptyline (Pamelor) 75–150 mg qd Protriptyline (Vivactil) 10 mg tid
TRICYCLIC ANTIDEPRESSANTS (TCAs) Maximum Dose
Amitriptyline (Elavil) 300 mg/day Amoxapine (Asendin)600 mg/day Clomipramine (Anafranil) 250mg/day Desipramine (Norpramin) 300 mg qd Doxepin (Sinequan) 300 mg qd Nortriptyline (Pamelor) 200 mg qd Protriptyline (Vivactil) 60 mg/day
- TCA Mechanism of Action
SNRI: They act by inhibiting both serotonergic and noradrenergic reuptake. This lengthens the time serotonin and norepinephrine remain in the synaptic cleft, enhancing their neurotransmission
Why are TCA good choice for treating depression in the patient with chronic pain?
The analgesic properties of TCAs are independent of their treatment effects on depression, thus making them a good choice for treating depression in the patient with chronic pain
Side Effects of TCA
Amitriptyline and imipramine are more sedating, with more weight gain and orthostatic hypotension. Other
anticholinergic side effects include dry mouth, constipation, blurred vision, urinary retention, sexual side effects, excessive sweating, and confusion or delirium. TCAs also decrease the seizure threshold. Desipramine and nortriptyline have fewer anticholinergic side effects, and of all of the TCAs, desipramine has the fewest anticholinergic side effects
How are TCAs monitored?
Serum plasma levels can be monitored for TCAs, and this is particularly important for desipramine, imipramine,
and nortriptyline, which have the best correlation of blood levels to therapeutic antidepressant response.
The therapeutic blood level for nortriptyline, desipramine and imipramine,
The therapeutic blood level for nortriptyline ranges from 50 to 150 ng/ml, and is 75 to 225 ng/ml for both desipramine and imipramine, as desipramine is simply the desmethyl metabolite of imipramine
- Prior to initiating treatment patients should have laboratory screening of
electrolytes, BUN, creatinine, and LFTs. TCAs also have quinidine-like properties, are potentially proarrhythmic, and can prolong the QTC interval
For those taking TCA, patients aged over 40 years, or with any history of cardiac disease should have
a baseline EKG, with particular attention to the QTC interval, checking that it is less than 450 ms
How is TCA metabolized?
TCAs are strongly protein-bound (85% to 95%) and undergo first-pass hepatic metabolism. Subsequent
stages involve demethylation, oxidation, and glucuronide
conjugation. Amitriptyline is demethylated to nortriptyline,
and imipramine is demethylated to desipramine
What should TCAs not be prescribed with and why?
Hepatic clearance involves the P450 enzyme system, and so drugs such as SSRIs, cimetidine, and methylphenidate increase TCA plasma levels. SSRIs and TCAs should not be prescribed at the same time unless plasma levels are carefully monitored
What drugs decrease serum TCA levels and why?
Phenobarbital, carbamazepine, and cigarette smoking induce the P450 enzyme system, and thus decrease serum TCA levels
How should TCA be dosed?
to minimize side effects and increase adherence initiation of TCAs should begin at lower doses (usually 25 mg for a week) than the target doses for antidepressant effect (typically 75–150 mg. The elderly are more sensitive to their side effects, so begin at doses of 10 to 20 mg in this age group.
abrupt discontinuation of TCAs causes
A withdrawal syndrome with abrupt discontinuation of TCAs, characterized by fever, sweating, headaches, nausea, dizziness, or akathisia
TCA overdose leads to
overdose
lethal. TCA overdose is a leading cause of drug related
overdose and death. 3-5x the therapeutic dose is potentially lethal, so this narrow therapeutic range must be respected, and blood levels serially done. Toxicity results from anticholinergic and proarrhythmic effects, such as seizures, coma, and QTC widening
TCAs effective for what pain syndromes?
TCAs have been shown to be modestly effective for diabetic
neuropathy pain, chronic regional pain syndrome, chronic headache, poststroke pain, and radicular pain. TCAs are useful as preemptive analgesics, being opioid-sparing in the postoperative period
the typical doses for the analgesic benefit of TCAs
(25 to 75 mg) are lower than the typical doses for antidepressant effect (75 to 150 mg)
SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
Milnacipran (Savella®)
SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
Usual Start Dose
Bupropion (Wellbutrin) 75 mg bid Duloxetine (Cymbalta) 30 mg qd Mirtazapine (Remeron)15 mg qhs Nefazodone (Serzone) 100 mg bid Trazodone (Desyrel) 50 mg qhs Venlafaxine (Effexor) 37.5 mg qd
SEROTONIN-NOREPINEPHRINE REUPTAKE
INHIBITORS (SNRIs)
Average Dose
Bupropion (Wellbutrin) 100–150 mg bid Duloxetine (Cymbalta) 60mg qd Mirtazapine (Remeron) 30-45mg qd Nefazodone (Serzone) 100–300 mg bid Trazodone (Desyrel) 100–250 mg bid Venlafaxine (Effexor) 75–112.5 mg bid
SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
Maximum Dose
Bupropion (Wellbutrin) 600 mg qd Duloxetine (Cymbalta) 120mg Mirtazapine (Remeron) 60mg qd Nefazodone (Serzone) 600mg/day Trazodone (Desyrel) 600mg/day Venlafaxine (Effexor) 375mg/day
SNRI Mechanism of Action
act by inhibiting serotonin and
norepinephrine reuptake
Milnacipran (Savella®)
approved for the treatment of
fibromyalgia but not depression
