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
Why does SNRI have fewer side effects than the tricyclics?
Lesser alpha-1, cholinergic, or histamine inhibition in this class of drugs results in fewer side effects than the tricyclics, with equivalent antidepressant and potentially equal analgesic benefits
superior analgesic properties of TCAs (particularly amitriptyline), which may be due
to their properties of NMDA antagonism and sodium channel blockade, in addition to their combined serotonin and norepinephrine reuptake inhibition
In patients taking venlafaxine,
caution should be taken in patients with
hypertension. Particularly at doses over 150 mg/day, venlafaxine may increase systolic blood pressure by 10 mm or more. This is likely due to the onset of norepinephrine
reuptake inhibition, which occurs at higher doses of venlafaxine that appear to be needed for analgesic efficacy in neuropathic pain
venlafaxine side effects
side effects include
nausea, somnolence, dry mouth, dizziness, nervousness,
constipation, anorexia, or sexual dysfunction.
In what patient is venlafaxine beneficial?
Many patients are unable to
tolerate the side effects of tricyclics, so venlafaxine and
duloxetine are promising agents in patients with major
depression and chronic pain
Duloxetine (Cymbalta) is an SNRI approved for use in the United States for
diabetic peripheral neuropathic
pain, fibromyalgia, major depression, and generalized
anxiety disorder
Duloxetine (Cymbalta) Side Effects
Dosing in the evening tends to mitigate the side effects of nausea and tiredness. Other side effects include dry mouth, dizziness, constipation, or sexual dysfunction. Dosing in the elderly should begin lower, such as 20 mg/day, due to increased
side effects and less tolerability
Bupropion mechanism of action
Bupropion is a noradrenergic and dopaminergic reuptake
pump inhibitor, prolonging the time norepinephrine and
dopamine remain in the synaptic cleft
Bupropion works for what conditions
has significant psychostimulant
properties. It is used in the treatment of depression,
ADHD, and smoking cessation, at doses up to 600 mg/day
How is Bupropion dosed?
Treatment should start at 75 to 100 mg in the morning to
avoid insomnia that may occur if the drug is started at night.
After 5 days, this dose is advanced to the average treatment dose of 100 to 150 mg bid, even for sustained-release preparations. At these doses there is a very slight decrease in seizure threshold. Doses from 450 to 600 mg/day may cause seizures in 4% of patients, so these doses should be avoided
Bupropion should not be prescribed to patients with
seizures, eating disorders, or those taking MAOIs. Caution
is needed in co-prescribing bupropion with tramadol since
the lowering of seizure threshold is most likely additive
Bupropion Side effects
Side effects include nervousness, headache, irritability, and insomnia
Mirtazapine
antidepressant with antagonism of serotonin and central presynaptic alpha2-adrenergic receptors, stimulating serotonin and norepinephrine release. This serves to potentiate serotonergic and noradrenergic
transmission, while having no anticholinergic effects.
Mirtazapine dosing
thought to preferentially augment serotonergic transmission and have an antihistaminic effect at lower doses, 15 to 30 mg/day. At higher doses, 45 to 60 mg/day, it augments more noradrenergic transmission
Mirtazapine side effects
As a result, at lower doses it is more sedating and has antianxiety effects, with the side effect of weight gain. At higher doses it is more activating and can provoke anxiety symptoms. Agranulocytosis and neurotropenia can rarely occur
Trazodone
a serotonin-2 antagonist/ reuptake inhibitor
(SARI), and is used for major depression and insomnia
Trazodone use
Trazodone is most often prescribed for insomnia that accompanies depressive,
anxious, or pain symptoms and is the preferred treatment
for insomnia
Trazodone Side Effects
A rare but serious side effect of trazodone is priapism, occurring in 1 in 1000 to 1 in 10,000 cases. Side effects common to both medications are sedation, dizziness, dry mouth, orthostatic hypotension, constipation, and headache
Anxiety disorders
generalized anxiety disorder, panic disorder, obsessive compulsive disorder, and PTSD
Pain-specific anxiety as well as generalized anxiety amplify
pain perception and pain complaints through several biopsychosocial mechanisms, including
sympathetic arousal
with noradrenergically mediated lowering of nociceptive threshold, increased firing of ectopically active pain neurons, excessive cognitive focus on pain symptoms, and poor
coping skills.
Pathologic Anxiety
are often restless, fatigued and irritable and have poor concentration. They may have muscle tension and sleep disturbances. Their mood is often low, but not at the severity level found
in MDD
best treatment outcomes for anxiety disorders
Overall, cognitive behavioral therapy demonstrates the
best treatment outcomes for anxiety disorders. Significant
improvements are further obtained with relaxation therapy, meditation, and biofeedback
most useful in the initial treatment stages to stabilize a disorder
Anxiolytics, such as benzodiazepines and buspirone,
Why are benzodiazepines poor choice for long-term treatment?
the side effects and physiologic dependency associated with them
Use of Antidepressants to treat anxiety
Antidepressants are useful in diminishing the overall
level of anxiety and preventing anxiety or panic attacks, but they have no role in treating acute anxiety. Both the SSRIs and SNRIs are effective agents among antidepressants.
SSRI dose in treating anxiety
Effective doses for SSRIs are higher than those for depression, typically 60 to 80 mg/day.
TCA used to treat obsessive compulsive disorder
Of the TCAs, clomipramine is the most effective, with
particular usefulness in obsessive compulsive disorder
Antidepressants that are used to treat anxiety
Nefazodone has antianxiety effects, as does venlafaxine at
higher doses. Mirtazapine has anxiolytic properties at the
lower, more sedating doses, and higher doses of 45- 60 mg can worsen anxiety with its activating qualities.
Why is Bupropion not used to treat anxiety?
Similarly, while there are reports that bupropion is effective in depressions with anxious features, its stimulating effects make it less attractive as a primary antianxiety agent
SNRIs used to treat anxiety
SNRIs, specifically venlafaxine and duloxetine, have
also demonstrated efficacy in generalized anxiety
Benzodiazepines (BZDs)
Half- life (hrs)
Alprazolam (Xanax) 6-20 Chlordiazepoxide (Librium) 30-100 Clonazepam (Klonopin) 18-50 Clorazepate (Tranxene) 30-100 Diazepam (Valium) 30-100 Estazolam (ProSom) 10-24 Flurazepam (Dalmane) 50-160 Lorazepam (Ativan) 10-20 Midazolam (Versed) 2-3 Oxazepam (Serax) 8-12 Temazepam (Restoril) 8-20 Triazolam (Halcion) 1.5-5
BENZODIAZEPINES (BZDs), BUSPIRONE
These medications are useful in the treatment of acute anxiety, panic attacks, and the stabilization of generalized
anxiety
BENZODIAZEPINES Mechanism of Action
BZDs bind to the BZD component of the
gamma-aminobutyric acid (GABA) receptor, an inhibitory neurotransmitter.
Effect of BENZODIAZEPINES on CNS
They depress the CNS at the levels of the limbic system, brainstem reticular formation, and cortex
Use of BENZODIAZEPINES
also used as muscle relaxants and to treat pain associated with muscular spasticity
Acute anxiety or panic attacks can be treated with short-acting BZDs, such as
lorazepam 0.5 to 2 mg q6hr, prn, which has a rapid onset of action (10 to 15 min) and a half-life of 10 to 20 hr
Why should caution be taken in prescribing short half-life drugs, such as alprazolam.?
While it has a rapid onset of action, it typically lasts only 2 to 3 hr and many patients have significant rebound anxiety, resulting in a rollercoaster of peaks and valleys of anxiety during the day
Buspirone
Buspirone is also an effective anxiolytic. It acts as a serotonin agonist
Buspirone useful in treating patients with
a history of substance abuse who may abuse BZDs
Buspirone dosing
It is started at 5 mg tid and can be advanced as high as 10 mg tid
How long does it take Buspirone to have anti-anxiety benefits?
buspirone requires 1 to 4 weeks of administration for antianxiety benefits
to appear
Buspirone Adverse Effect
Patients can experience headache, dizziness,
paresthesias, and GI upset
Clonazepam dose
0.25 to 1 mg tid, a long-acting BZD, is often used in conjunction with a short-acting agent or an antidepressant to stabilize persistent anxiety or prevent acuteanxiety attacks
Side Effects of Benzodiazepines
all of the BZDs can cause profound sedation, confusion, or respiratory depression, and can be fatal in overdose
How to deal with physical and psychological dependence of Benzodiazepines?
long tapering schedules from 1 to 3 months to minimize withdrawal symptoms
Abrupt discontinuation of Benzodiazepines can cause
insomnia, anxiety, delirium, psychosis, or seizures
Mood stabilizers are agents that possess both
antimanic and antidepressant properties
MOOD STABILIZERS
AND ANTIEPILEPTICS indications
This class of medications is often used to treat patients with chronic neuropathic pain, trigeminal neuralgia, and headache
MOOD STABILIZERS
AND ANTIEPILEPTICS
Lithium,
Valproic Acid (Depakote Carbamazepine
(Tegretol®)
lamotrigine (Lamictal®)
Anticonvulsants acts as analgesics for
neuropathic pain and headache prophylaxis
Lithium
Lithium is the most commonly prescribed mood stabilizer for bipolar disorder and is the only one demonstrating a clear decrease in suicide attempts
lithium has been used as prophylaxis for
chronic daily headaches and cluster headaches
Why does Lithium levels need to be monitored?
Lithium has a narrow therapeutic range for both benefit and toxicity,
thus obtaining serum levels is important. Lethal overdoses
can involve as little ingestion of 4 to 5 times the daily dose
Lithium has effects on what organs?
Lithium has effects on the thyroid and kidney,
and their function must be monitored
Depakote
Depakote is the brand name of long-acting valproic acid,
with a duration of action of 8 to 12 hr
Depakote Effects
antimanic and antidepressant effects
Depakote Use
Depakote can also be
used for the treatment of impulsivity and aggression. use in migraine prophylaxis,
and seizure treatment.
Depakote doses
Starting dose is 250 mg/day and a typical
dose used in pain medicine is 250 mg tid, while doses used
in treatment of bipolar disorder are higher, 500 to 1000 mg tid
Blood tests in patient taking Depakote
Serum levels are monitored for therapeutic and toxicity ranges. Prior to initiating treatment, CBC and liver function tests are done
Depakote Adverse Effects
Anemia and neurotropenia are rare side effects of valproic acid, but thrombocytopenia is more common
How is thrombocytopenia monitored in patient taking Depakote?
Platelet levels should be checked at least 2 weeks after the start of treatment and 2 weeks after reaching a therapeutic dose. Fortunately, platelet levels quickly rise
after discontinuation of valproic acid
Adverse Effects of Depakote
Sedation, dizziness,
and hepatitis are other side effects.Hepatotoxicity/ hepatic failure and pancreatitis are also rare but serious potential
side effects. As a result, this medication is contraindicated in patients with hepatic disease
Depakote in Pregnancy
This medication should
not be given to pregnant women, as it is associated with neural tube defects
Lamotrigine (Lamictal)
an antiepileptic medication very commonly prescribed
for seizure control by neurologists and for mood stabilization
by psychiatrists
Lamotrigine use
It is often prescribed for bipolar patients with prominent depressive symptomatology and
it appears to be more effective in preventing depression than mania. use as a preventive
agent in headache management, reducing the frequency of migraines.
Lamotrigine Adverse Effects
rash may occur in up to 10% of individuals and
Steven-Johnson syndrome, also known as toxic epidermal
necrolysis, has been reported in 0.08% of individuals
Lamotrigine Dose
this medication
is often started 25 mg daily for 2 weeks, then 50 mg daily for 2 weeks, 100 mg daily for 1 week, and then 200 mg
daily for most patient
Carbamazepine( Tegretol)
is an anticonvulsant
used to treat partial seizures and generalized seizures
Carbamazepine Indications
well-established mood stabilizer and is also
the first-line treatment for trigeminal neuralgia and other neuropathic pain disorders with a lancinating quality
Carbamazepine Doses
This medication is usually started at doses between 200 and
400 mg daily in divided doses with a therapeutic dose range of 750 to 2500 mg daily in divided dose
Carbamazepine Adverse Effects
serious side effects including rash, agranulocytosis, and aplastic anemia necessitating regular lab monitoring
NEUROLEPTICS
(antipsychotics) indications
used to treat any psychotic process, the hallmark illness being schizophrenia, and
psychotic symptoms in depression, mania, or delirium
NEUROLEPTICS serious side effects
Parkinsonism and tardive dyskinesia have limited their use in pain medicine (particularly for the older generation
of antipsychotics such haloperidol (Haldol®) or fluphenazine (Prolixin®)
different types of pain treated by antipsychotics
cancer pain and chronic non cancer pain, such as fibromyalgia, chronic headache, low back pain, musculoskeletal pain, chronic pain in older patients, chronic facial
pain, and diabetic neuropathy
Possible mechanism of antipsychotic pain relief
It may be that antidopaminergic properties play a role in analgesia, whereas the serotoninergic antagonism may also be important for pain relief. Antipsychotic
antagonism of alpha2-adrenoceptors may also mediate
analgesia.
Typical neuroleptics
Usual Dose
Fluphenazine (Prolixin) 5–10 mg bid-tid Haloperidol (Haldol) 2–5 mg bid-tid Perphenazine (Trilafon) 8–16 mg bid-tid Thiothixene (Navane) 5–10 mgtid Trifluoperazine(Stelazine) 5–10 mg bid Loxapine (Loxitane) 20–50 mg bid-tid Chlorpromazine (Thorazine) 10–50 mg bid-qid Thioridazine (Mellaril) 100–200 mg bid-qid
Typical neuroleptics
Maximum Dose
Fluphenazine (Prolixin) 40 mg/day Haloperidol (Haldol) 100 mg/day Perphenazine (Trilafon) 64 mg/day Thiothixene (Navane) 60 mg/day Trifluoperazine(Stelazine) 40 mg/day Loxapine (Loxitane) 250 mg/day Chlorpromazine (Thorazine) 2000 mg/day Thioridazine (Mellaril) 800 mg/day
Typical neuroleptics
act as antipsychotics
through their antagonism of dopamine receptors, particularly the D2 receptors. They also have actions on histaminic, cholinergic, and alpha-1 adrenergic receptors
Prototypical Typical neuroleptics
Haloperidol is the prototypical agent in this class, with a molecular structuresimilar to morphine
Adverse Effects of typical neuroleptics
All of the typical neuroleptics have
varying degrees of anticholinergic side effects: dry mouth,
dizziness, sedation, weight gain, constipation, or blurred vision. They are also plagued by varying degrees of extrapyramidal
effects: tremor, dystonia, akathisia, and, most seriously, tardive dyskinesia, which is permanent
Effects of typical neurolptics on seizure threshold
All of these
agents very slightly lower the seizure threshold and may
elevate serum glucose levels.
Cardiovascular effects of typical neurolptics include
hypotension, tachycardia, nonspecific EKG changes (including
torsades de pointes), and, exceedingly rare, sudden cardiac death
Atypical Neuroleptics
Usual Dose
Aripiprazole) Abilify 5 mg qd Clozaril) Clozapine 100–300 mg qd-bid (Zyprexa) Olanzapine 5–15 mg qd Seroquel) Quetiapine 50–150 mg bid-tid (Risperdal) Risperidone 2–4 mg qd-bid Geodon) Ziprasidone 20–40 mg bid
Atypical Neuroleptics
Maximum Dose
Aripiprazole) Abilify 30 mg qd Clozaril) Clozapine 900 mg/day (Zyprexa) Olanzapine 20 mg/day Seroquel) Quetiapine 800 mg/day (Risperdal) Risperidone 16 mg/day Geodon) Ziprasidone 160 mg/day
Clozapine used in treatment of
refractory schizophrenia
Compare typical and atypical neuroletics
The atypicals have a lesser degree of dopamine D2 receptor antagonism and a greater degree of D4 receptor antagonism than the typical neuroleptics. they have some degree of serotonin-2 receptor blocking.
Mixed receptor profile of atypical neuroleptics results in
far fewer extrapyramidal, anticholinergic, and cardiac side effects
Why use caution in prescribing atypical neuroleptics in patients with diabetes?
Emerging evidence indicates that the atypicals, particularly olanzapine, lower
glucose tolerance and can elevate serum glucose levels.
Adverse Effects of atypical neuroleptics
varying degrees of anticholinergic side effects: dry mouth,
dizziness, sedation, weight gain, constipation, or blurred vision. They are also plagued by varying degrees of extrapyramidal
effects: tremor, dystonia, akathisia, and, most seriously, tardive dyskinesia, which is permanent
Compare typical and atypical neuroletics in treatment of symptoms
Both classes are equally as effective for the “positive symptoms” of psychosis: hallucinations and delusions. However, the atypicals are more effective for the “negative symptoms:” flat affect, poor motivation, and social withdrawal
Olanzapine (Zyprexa®)
has been shown to provide pain relief from what receptor?
alpha2- adrenoceptors, opioid, and serotonergic receptor activity
