Chapter 15 Psychopharmacology for Pain Medicine Flashcards Preview

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Flashcards in Chapter 15 Psychopharmacology for Pain Medicine Deck (151):

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.



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

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



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


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


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



Amitriptyline (Elavil)
Amoxapine (Asendin)
Clomipramine (Anafranil)
Desipramine (Norpramin)
Doxepin (Sinequan)
Nortriptyline (Pamelor)
Protriptyline (Vivactil)


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


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


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

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)



Duloxetine (Cymbalta)
Venlafaxine (Effexor)
Milnacipran (Savella®)


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


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


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


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



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



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



These medications are useful in the treatment of acute anxiety, panic attacks, and the stabilization of generalized


BENZODIAZEPINES Mechanism of Action

BZDs bind to the BZD component of the
gamma-aminobutyric acid (GABA) receptor, an inhibitory neurotransmitter.



They depress the CNS at the levels of the limbic system, brainstem reticular formation, and cortex



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 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



This class of medications is often used to treat patients with chronic neuropathic pain,
trigeminal neuralgia, and headache



Valproic Acid (Depakote Carbamazepine
lamotrigine (Lamictal®)


Anticonvulsants acts as analgesics for

neuropathic pain and headache prophylaxis



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 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


(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


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
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

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