PEP Topic 
Chronic Pain

Antidepressants are a class of medications to treat depression. They include subgroups of tricyclic antidepressants (i.e., older drugs, those with a high incidence of anticholinergic effects, and drugs that are highly cardiotoxic in overdose) such as desipramine, nortriptyline, amitriptyline, imipramine, doxepin, and clomipramine; selective serotonin reuptake inhibitors (SSRIs), newer drugs with fewer severe side effects, including fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, and escitalopram; serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (duloxetine is most common); psychostimulants (methylphenidate is most common); and others (e.g., bupropion, trazodone, mertrazpine, mianserin*). Antidepressant use in patients with cancer has been evaluated in depression and anxiety and as adjunctive treatment in pain. Specific antidepressants have also been evaluated in peripheral neuropathy.

* Not available in the United States

Effectiveness Not Established

Guideline/Expert Opinion

Miaskowski, C., Cleary, J., Burney, R., Coyne, P., Foster, R., Grossman, S., . . . Zahrbock, C. (2005). Guideline for the management of cancer pain in adults and children. APS Clinical Practice Guidelines Series. Glenview, IL: American Pain Society.


Type of Resource/Evidence-Based Process:

PROCESS OF DEVELOPMENT: An interdisciplinary panel of experts in cancer pain management prepared these guidelines. When unavailable, recommendations were not made or were made on the recommendation of experts in that area.

Results Provided in the Reference:

Type of Evidence: Meta-analysis of multiple, well-designed, controlled studies

Guidelines & Recommendations:

Cancer Pain
  • Make patient and family caregiver education about pain management a part of the treatment plan, and encourage patient and family caregivers to participate actively in pain management. 
  • Collaborate with patients and family caregivers, taking costs and availability of treatment options into account when selecting pain management strategies. (Panel consensus)
  • Perform a comprehensive pain assessment of all patients with cancer at each outpatient visit or hospital admission and use each patient’s self-report as the foundation for the assessment. 
  • Include in the comprehensive pain assessment a detailed history to determine the presence of persistent and breakthrough pain and its effects on function; a psychosocial assessment; a physical examination; and a diagnostic evaluation of signs and symptoms associated with common cancer pain presentations and syndromes. 
Cancer Pain Management
  • Develop a systematic approach to cancer pain management and teach patients and family caregivers how to use effective strategies to achieve optimal pain control.
  • Begin a bowel regimen to prevent constipation when the patient is started on an opioid analgesic. 
  • Administer a long-acting opioid on an around-the-clock basis, along with an immediate-release opioid to be used on an as-needed basis, for breakthrough pain once the patient’s pain intensity and dose are stabilized. 
  • Do not use meperidine in the management of chronic cancer pain. 
  • Adjust opioid doses for each patient to achieve pain relief with an acceptable level of side effects. 
  • Avoid intramuscular administration because it is painful and absorption is unreliable.
  • Use optimally titrated doses of opioids and maximal safe and tolerable doses of coanalgesics through other routes of administration before considering spinal analgesics. (Panel consensus)
  • Monitor for and prophylactically treat opioid-induced side effects.
  • Clarify myths and misconceptions about pain management, and reassure patients and family caregivers that cancer pain can be relieved and that addiction and tolerance are not problems associated with effective cancer pain management.
  • Use cognitive and behavioral strategies as part of a multimodal approach to cancer pain management, not as a replacement for analgesic medications.
Management of Procedure-Related Pain in Children and Adults
  • Offer patients who decline to have procedural sedation nonpharmacologic alternatives to decrease procedure-related pain. 
Quality Improvement in Cancer Pain Management
  • Implement a formal process to evaluate and improve the quality of cancer pain management across all stages of the disease process and across all practice settings. 
  • Evaluate the quality of cancer pain management at points of transition in the provision of services (e.g., from the hospital to the home) to ensure that optimal pain management is achieved and maintained. 

National Comprehensive Cancer Network. (2011). NCCN Clinical Practice Guidelines in Oncology: Adult cancer pain [v. 2.2011]. Retrieved from

Type of Resource/Evidence-Based Process:

These guidelines do not provide any information about search strategy or any specific evaluation of evidence. Notes state that most direct evidence is of low quality, but recommendations do result from unanimous consensus.

Guidelines & Recommendations:

The guidelines provide detailed recommendations regarding:

  • Screening and assessment
  • Management of pain in opioid-naive as well as opioid-tolerant patients
  • Ongoing care of adult patients with cancer and related pain management
  • Comprehensive pain assessment and use of pain ratings
  • Interventions for specific types of pain syndromes
  • Opioid prescribing, titration, and ongoing management
  • Management of adverse effects related to opioids
  • Psychosocial support and patient and family education
  • Nonpharmacologic interventions.


In general, opioids are first-line interventions. The NCCN guidelines suggest that antidepressants and anticonvulsants can be first-line treatments for adjuvant pain, although the recommendation for using them as such is still based on anecdotal experience or guidelines relating to patients who do not have cancer.

Nursing Implications:

The NCCN guidelines provide comprehensive algorithms for pain management, from screening to ongoing maintenance. The guidelines recommend considering a variety of nonpharmacologic interventions. Psychosocial support, including coping-skills training, is recommended, as is comprehensive patient and family education. The guidelines provide useful information and an overview of the full range of pain management. The work points to the ongoing need to consider multiple adjuvant and supportive interventions to achieve pain relief that works for the individual patient.

Research Evidence Summaries

Banerjee, M., Pal, S., Bhattacharya, B., Ghosh, B., Mondal, S., & Basu, J. (2013). A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy. Indian Journal of Pharmacology, 45, 334–338.

doi: 10.4103/0253-7613.115000

Study Purpose:

To determine the comparative efficacy and safety of gabapentin and amitriptyline as coanalgesics for cancer-related pain

Intervention Characteristics/Basic Study Process:

Patients were assigned randomly to receive oral tramadol 150–200 mg and oral gabapentin titrated from 600–1,800 mg daily, or tramadol 150–200 mg and amitriptyline titrated from 25–100 mg daily. Oral morphine or fentanyl transdermal patch were used as rescue medication. At baseline, if patients were on any coanalgesic, they were entered after a washout period. Patients were followed monthly up to six months. Patients were asked to maintain a diary used for assessment of compliance. Once a patient used rescue medication, the patient was excluded from further efficacy assessment, and last pain scores were carried forward.

Sample Characteristics:

  • N = 76  
  • MALES: 53%, FEMALES: 47%
  • KEY DISEASE CHARACTERISTICS: Tumor types are not stated. Baseline pain scores were 8.425 on average.
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients did not have any disorder of vital organs or bone marrow.


  • SITE: Single site   
  • SETTING TYPE: Outpatient   
  • LOCATION: India

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Late effects and survivorship
  • APPLICATIONS: Palliative care

Study Design:

  • Open-label, two-group, randomized trial

Measurement Instruments/Methods:

  • Visual analog scale (VAS)—scored as 0, 1, or 2 if scores decreased, remained the same, or increased
  • Verbal rating scale (VRS)
  • Percentage of pain relief (PPR) calculated
  • Global pain score calculated as the sum of changes in VAS score, VRS score, and PPR
  • MD global impression of efficacy (four-point scale)


For patients receiving gabapentin, pain scores on the VAS reduced significantly between the first and second month (p < .001). The same timing and pattern of pain reduction were shown in the amitriptyline group (p < .001). No significant differences were seen between groups at any study time point. Six patients on gabapentin and eight patients receiving amitriptyline required rescue medication. Thirty percent of patients in the gabapentin group and 42% of patients in the amitriptyline group had adverse events. These were generally mild. More patients receiving amitriptyline experienced postural hypotension (p = .02) and dry mouth (p = .04). Sedation, dizziness, and dyspepsia were the most frequent side effects.


Findings suggest that gabapentin and amitriptyline can be effective as coanalgesics for neuropathic pain.


  • Small sample (less than 100)
  • Risk of bias (no blinding)
  • Unintended interventions or applicable interventions not described that would influence results
  • Measurement validity/reliability questionable
  • Findings not generalizable
  • Subject withdrawals 10% or more
  • Other limitations/explanation: Information regarding any changes in opioid medications or lack of change is not provided. No data regarding compliance are provided. Depending on the timing in which patients who used rescue medication had prior pain scores carried forward, this approach could have overestimated or underestimated results. Opioid dosage information is not provided. The sample did not appear to have any significant comorbid conditions, so applicability among patients with other chronic diseases is unclear.

Nursing Implications:

Findings suggest that either gabapentin or amitriptyline can be effective coanalgesics for neuropathic pain, and professional guidelines generally have suggested consideration of such medication. The side effect profiles of the two drugs studied here were slightly different, so individual patient characteristics and risks need to be considered in medication selection. In this study, patients had no significant other disorders, so if similar results would be seen among patients with comorbid conditions is not clear.