Chronic pain is frequently comorbid with both anxiety and mood disorders. Although many pain medicine practitioners may not manage psychiatric conditions, it is increasingly important to have at least a rudimentary familiarity with first-line psychiatric medications used to treat anxiety and mood disorders, a class of medications that is commonly encountered by pain specialists.
The mnemonic AMPS, or anxiety, mood, psychosis, and substance abuse, can be used to describe which psychiatric conditions are more commonly seen in the outpatient setting. In this chapter, we focus on the medication management of anxiety and mood (including major depressive disorder and bipolar spectrum disorders) because these disorders often influence the short- and long-term prognosis of those with chronic and unexplained pain. Antipsychotic medications are also discussed because there is much overlap with this class and the treatment of bipolar disorder. Tables 76-1 and 76-2 provide a practical overview of these medications.
Overview of the First-Line Antidepressants
Class | Initial Dose (mg/day) | Therapeutic Dose (mg/day) | Clinical Highlights |
Selective Serotonin Reuptake Inhibitors | |||
Sertraline | 50 | 50–200 | Serotonin and dopamine reuptake inhibition Possible early and temporary diarrhea and dyspepsia Relatively low chance for drug interactions |
Paroxetine | 20 | 20–60 | High anticholinergic and antihistamine side effect profile |
Paroxetine CR | 12.5–20 | 25–75 | High risk for sedation, weight gain, and dry mouth Short half-life with more risk for discontinuation syndrome High chance for drug interactions Unsafe during pregnancy (Category D) |
Fluoxetine | 20 | 20–60 | Long half-life and ideal for intermittently compliant patients Relatively inexpensive High chance for drug interactions |
Citalopram | 20 | 20–40 | Structurally similar to escitalopram Decreased chance for drug interactions Warning for QTc prolongation above 40 mg/day |
Escitalopram | 10 | 10–20 | Structurally similar to citalopram Decreased chance for drug interactions Warning for QTc prolongation |
Vilazodone | 10 | 40 | Increase dose every week by 10 mg, as tolerated and to effect Must be taken with a meal in order to be fully bioavailable Moderate-to-high potential for CYP 3A4 drug interactions |
Serotonin–Norepinephrine Reuptake Inhibitors | |||
Venlafaxine XR | 37.5 | 75–225 | Structurally similar to desvenlafaxine (do not use concurrently) Dual action on serotonin and norepinephrine receptors Not consistently “activating” but usually does not cause sedation Sometimes used as an adjunct for chronic pain Avoid in those with difficult-to-treat hypertension Short half-life with more risk for discontinuation syndrome Reduce dose with renal insufficiency |
Desvenlafaxine | 50 | 50–100 | Structurally similar to venlafaxine (do not use concurrently) Dual action on serotonin and norepinephrine receptors Not consistently “activating” but usually does not cause sedation Avoid in those with difficult-to-treat hypertension Short half-life with more risk for discontinuation syndrome Sometimes used to treat neuropathic pain syndromes Reduce dose with renal insufficiency |
Duloxetine | 30 | 20–60 | Dual action on serotonin and norepinephrine receptors Not consistently “activating” but usually does not cause sedation Approved for treatment of pain conditions Short half-life with more risk for discontinuation syndrome Increased risk for drug interactions |
Atypical | |||
Bupropion XL | 150 | 300–450 | Given once daily with likely increased adherence to treatment Dual action on dopamine and norepinephrine receptors Contraindicated with seizure and eating disorders Increased risk for seizures in those with alcohol or benzodiazepine withdrawal Not used for anxiety disorders May worsen anxiety associated with depression No serotonin activity and no related sexual side effects |
Mirtazapine | 15 | 15–45 | Dual action on serotonin and norepinephrine receptors Decreased frequency of sexual side effects Increased sedation and sleepiness at mainly lower doses May be associated with significant increase in appetite and weight gain Although not indicated for anxiety disorders, it may be helpful |
Overview of the Mood Stabilizers
| Starting Dose* | Target Serum Level | Titration Schedule | Side Effects | Monitoring |
Lithium | 300 mg BID/TIDMay be dosed QHS if tolerated | 0.6–1.2 mEq/L (acute mania) | Steady-state level reached in 4–5 days Increase by increments of 300–600 mg/day, as tolerated | Nausea or vomiting, diarrhea, tremor, fatigue, polyuria, acne, worsened psoriasis, diabetes insipidus ECG changes (mainly benign T-wave changes) Hypothyroidism Toxicity (confusion, ataxia, dysarthria, coma) High caution in those with renal insufficiency Potentially lethal because of its narrow therapeutic window Pregnancy Category D | Check lithium level 5–7 days after each dose change Every 3 months: lithium level, TSH, metabolic panel Lithium toxicity risk increased by:
|
Valproate/divalproex Indicated for prophylactic treatment of migraine headaches | 500–1000 mg BID (25 mg/kg/day for acute mania) ER dosed 500–2000 mg QHS | 85–125 μg/mL | Steady-state level reached in 3–5 days Increase by 500–1000 mg/day, as tolerated | Sedation Tremor Weight gain Hypersensitivity Thrombocytopenia Transaminitis Hyperammonemia Encephalopathy Polycystic ovary syndrome Pancreatitis Pregnancy Category D | Baseline, 3-month, 6-month, and annually thereafter: VPA level, CBC, AST, and ALT |
Carbamazepine Indicated for trigeminal neuralgia | ER 200 mg BID | 6–10 μg/mL | Steady-state level reached in 3–4 days Increase by 200 mg/day (up to 1600 mg/day), as tolerated | Dizziness Somnolence Stevens Johnson syndrome Hyponatremia (SIADH) Leukopenia, pancytopenia, thrombocytopenia Hepatitis Drug interactions are common Pregnancy Category D | Baseline, 3-month, 6-month, and annually thereafter: carbamazepine level, CBC, serum chemistry, liver enzymes |
Oxcarbazepine | 300 mg BID | Not established for bipolar disorder | Increased by 300 mg/day, as tolerated | Fatigue Ataxia Hyponatremia Stevens Johnson syndrome Pregnancy Category C | Serum sodium during maintenance treatment (interval not established; consider every 3–4 months) |
Lamotrigine† | 25 mg/day | Not established for bipolar disorder | 25 mg/day for 2 weeks, then 50 mg/day for 2 weeks, then 100 mg/day for 1 week, then 200 mg/day (dose titration pack available), as tolerated‡ | Rash, Stevens Johnson syndrome Hepatitis Anemia, leukopenia, thrombocytopenia Pregnancy Category C | Signs of rash |
The following list illustrates the importance of including evidence-based psychiatric screening strategies and initiating timely and effective treatment for patients with depression and anxiety, within the context of providing care for those who have a severe or refractory pain condition(s).
At least one-half of all those referred for outpatient mental health care do not connect with a mental health provider. There are many reasons for this, including poor access to care and mental health–related stigma.1
Treatments of anxiety and mood disorders relieve “mental pain” and often have a therapeutic effect on “physical pain” disorders.
Some psychotropic medications are used as to treat primary pain conditions (e.g., norepinephrine reuptake inhibitors). A complete understanding of the indications for use, mechanism of action, and possible side effects is critical for pain medicine practitioners.2
The combination of severe and chronic pain, coupled with untreated depression and anxiety, can result in significant disability or possibly suicide. About one-half of all those who complete suicide have seen their non–mental health, medical provider 30 days before their death. About one-half of these cases result in litigation.3
The selective serotonin reuptake inhibitors (SSRIs) were developed in the 1980s and saw an explosion of use as safe, well tolerated, and effective treatments for depression. Now the SSRIs are indicated for a wide range of depressive and anxiety disorders, including major depression, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), social phobia, premenstrual dysphoric disorder, and bulimia nervosa. Since the introduction of Prozac in 1987, antidepressant prescribing has quadrupled, and antidepressants have become the third most commonly prescribed class of medications among Americans and the most commonly prescribed class among Americans aged 18 to 44 years. Psychiatrists prescribe less than one-third of these medications. Depression occurs comorbid with chronic pain in up to 60% of patients and can complicate the treatment and worsen the prognosis of pain. On the other hand, the successful treatment of depression can reduce pain perception. The safety and tolerability of the SSRIs make them an important tool for the pain practitioner.
Regardless of the drug, medication therapy is effective in the majority of moderate to severe cases of depression. Within approximately 6 weeks, one-half of persons receiving antidepressants have at least a 50% reduction in symptoms.4 In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 30% of patients achieved full remission after 12 weeks of treatment with citalopram, and 10% to 15% more showed significant improvement. One-quarter of patients who failed citalopram responded when switched to sertraline, venlafaxine, or bupropion. A similar number responded when bupropion was added to citalopram.5 Benefits of antidepressant therapy may take as little as 1 week or as long as 6 to 8 weeks to see. Unless intolerable, medications should not be changed or discontinued in the first 6 weeks of therapy for depression or anxiety (see Table 76-1).
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