Date: {{$ActivityAssignDate}}

Subject: A retrospective cross-sectional, observational survey study to analyze role of flexible dosing of Gabapentin + Amitriptyline FDC in patients with neuropathic pain not responding to monotherapy


Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. As such, pain is a warning about tissue damage signalled by specific receptors and fiber systems extending from the periphery to the brain. Pain can be experienced as an acute, chronic or intermittent sensation, or as a combination of the three, and is reported to be the common reason for medical visits. Acute pain, the most commonly experienced type of pain, may be a result of injuries, acute illnesses, surgeries or labor1.

The International Association for the Study of Pain (IASP) defines neuropathic pain as pain caused by a lesion or disease of the somatosensory nervous system.2 This definition replaces an older definition according to which neuropathic pain was “pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation of the peripheral or central nervous system”.3


Two changes are important in this change of definition: dysfunction and the neuronal lesion.

  1. In the new definition of neuropathic pain, dysfunction is no longer accepted as a criterion because it is difficult to accept symptoms and soft signs as criteria if they cannot be verified objectively.

  2. It is now specified that the lesion needs to affect the somatosensory system meaning that lesions or diseases outside the somatosensory pathways, e.g., the cerebellum, does not qualify as neuropathic.


Neuropathic pain is a chronic condition which represents a significant burden for patients, society and healthcare systems.4 The prevalence of neuropathic pain in the general population has been estimated at 6.9–10.0%.​5

Management includes effective pharmacotherapy options for patients with painful diabetic neuropathy like serotonin-norepinephrine reuptake inhibitors (duloxetine, venlafaxine), tricyclic antidepressants (amitriptyline, desipramine, nortriptyline), and gabapentinoid antiseizure medications (pregabalin, gabapentin). All have been shown to be more effective than placebo in randomized trials, and limited comparative data suggest that efficacy is similar across agents.

The four main reasons that treatments for neuropathic pain fail are:

  1. Inadequate diagnosis and a lack of appreciation of the mechanisms involved

  2. Insufficient management of psychological comorbid conditions

  3. Incorrect understanding or selection of treatment options

  4. Use of inappropriate outcomes measures


The goals of combination therapy in the management of neuropathic pain include:

  1. Adequate pain relief
  2. Reduction in adverse effects
  3. Improvement of treatment compliance
  4. Restoration of functional status.

Rationale

  • FDC of gabapentin and amitriptyline allows use of 2 drugs with different mechanism of action thus targeting multiple NP mechanism.
  • The combination may have additive effect resulting in enhanced pain relief compared to the use of either drug alone.
  • It also allows use of lower doses of individual drugs and thus may improve safety profile and patient compliance
  • The Delphi panel assessed the combination of pregabalin /gabapentin and TCAs as being well documented (CDC rating I + A) with added advantage of improving sleep disturbances.​6


Mechanism of action

Gabapentin The binding to α2δ-1 subunits inhibits nerve injury-induced trafficking of α1 pore forming units of calcium channels (particularly N-type) from cytoplasm to plasma membrane (membrane trafficking) of pre-synaptic terminals of dorsal root ganglion (DRG) neurons and dorsal horn neurons.​7 TCAs can be classified into tertiary amines (amitriptyline and imipramine) and secondary amines (nortriptyline and desipramine). These drugs block the reuptake of serotonin and norepinephrine thereby increase the availability of these inhibitory neurotransmitters in the descending pain pathway which assists in reducing the neuropathic pain.

Gabantin AT (Gabapentin 100/300 mg and Amitriptyline 10 mg) tablets are marketed by Sun Pharmaceutical Industries Ltd. Although every product is marketed only after regulatory approval, it is important to know how it performs in day-to-day practice of individual medical practitioners. For this purpose, we have planned to conduct a survey to analyze role of flexible dosing of Gabapentin + Amitriptyline FDC in patients with neuropathic pain not responding to monotherapy.

We invite you to participate in this data collection activity. All you need to do is to report on a standard form your experience with this combination drug in the normal course of your practice. If you agree to participate, you will need to fill data collection forms (which we call DCF).

We trust you and we are partners in promoting this well tolerated and effective drug therapy. In that spirit we hope you will consent to participate in this study. If you do, please sign and return the enclosed reply along with your visiting card for accuracy of records.





Yours truly,


Sun Pharma Laboratories Limited,