Anti-depressants vs Anti-convulsants for Chronic Pain

(SPEC-AA Trial)

Overseen By Vafi Salmasi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must not be taking: SSRIs

Disqualifiers: Patient refusal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 months

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether anti-depressants or anti-convulsants are more effective for people with chronic pain. Chronic pain, which lasts over three months, can significantly impact daily life. The study will compare these two types of medication in a real-world setting to determine which provides more relief. Individuals experiencing long-term pain and considering these medications with their doctor may be suitable candidates for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective; this research aims to understand how it benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, if you are on a large dose of a specific type of anti-depressant (SSRI), you might be excluded from the trial.

What is the safety track record for these treatments?

Research shows that both anti-seizure and anti-depressant medications can safely manage chronic pain, though they may have some side effects.

For anti-seizure medications like pregabalin, studies have found they are generally well-tolerated. Common side effects include dizziness, sleepiness, and headaches, but these usually don't last long. A small risk of experiencing suicidal thoughts or behavior exists, which is a concern with many medications in this category.

Regarding anti-depressants, duloxetine is noteworthy. Research has shown it to be safe and effective for treating pain. Like anti-seizure medications, duloxetine may slightly increase the risk of suicidal thoughts, especially when starting the medication. However, it is generally well-tolerated, and many people find it helpful for chronic pain.

These medications are often used in everyday settings, and the trial aims to improve their use for chronic pain. Always consult your healthcare provider about the potential risks and benefits before starting any new treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using anti-convulsant and anti-depressant medications for chronic pain because they offer a novel approach compared to standard painkillers. Unlike typical treatments like NSAIDs or opioids, anti-convulsants work by calming nerve activity, which can help manage pain tied to nerve damage. Anti-depressants, on the other hand, may alter neurotransmitters in the brain to decrease pain perception. This dual approach targets pain from different angles, potentially offering relief for those who don't find traditional pain medications effective.

What evidence suggests that this trial's treatments could be effective for chronic pain?

In this trial, participants will be randomized to receive either an anti-convulsant or an anti-depressant medication for chronic pain. Research has shown that anti-convulsant medications like pregabalin and gabapentin can significantly reduce chronic pain. Specifically, many patients in studies experienced a 30% to 50% decrease in pain with pregabalin. Gabapentin has also proven effective for long-term nerve pain, such as that caused by diabetes. Among anti-depressants, duloxetine stands out for its ability to reduce pain by 50% in chronic conditions. These medications not only alleviate pain but also enhance mood and overall quality of life. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic pain lasting more than 3 months, who could be treated with anti-convulsants or anti-depressants. Patients must have a balanced chance of benefiting from either medication as judged by their doctor. Those with conditions that prevent the use of these drugs or who refuse to participate are excluded.

Inclusion Criteria

The treating pain provider is unsure about the best choice between anti-convulsants and anti-depressants for your condition.

I have been experiencing pain for over 3 months.

My doctor recommends anti-convulsants or anti-depressants for my pain.

Exclusion Criteria

I have chosen not to participate in certain treatments or procedures.

I cannot take anti-convulsants or anti-depressants as advised by my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either anti-convulsant or anti-depressant medication for chronic pain management

6 months

3 visits (in-person) at 1, 3, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Observation

Data collection from patients who do not enter the randomization arms

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-convulsant medications
• Anti-depressant medications

Trial Overview The study compares the effectiveness of two common chronic pain treatments: anti-convulsant and anti-depressant medications. It involves randomly assigning patients to one treatment group during clinic visits using an open-source system called CHOIR, which tracks patient outcomes.

How Is the Trial Designed?

Group I: Anti-depressant medication Experimental Treatment 1 Intervention

The participants will be randomized to receiving an anti-depressant medication. Then using a patient centered approach, the participant and their treating pain provider will choose one medication within the class. Participants will continue the medications for at least 6 months provided that they can tolerate the side effects, consider the treatment effective, and are willing to continue the treatment. We are studying two classes of medications and specific names of medications do not apply.

Group II: Anti-convulsant medication Experimental Treatment 1 Intervention

The participants will be randomized to receiving an anti-convulsant medication. Then using a patient centered approach, the participant and their treating pain provider will choose one medication within the class. Participants will continue the medications for at least 6 months provided that they can tolerate the side effects, consider the treatment effective, and are willing to continue the treatment. We are studying two classes of medications and specific names of medications do not apply.

Anti-convulsant medications is already approved in European Union, United States for the following indications:

Approved in European Union as Lyrica for:

• Diabetic peripheral neuropathy
• Post-herpetic neuralgia
• Epilepsy

Approved in United States as Lyrica for:

• Diabetic nerve pain
• Post-herpetic neuralgia
• Partial seizures

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

Tricyclic antidepressants and certain novel antidepressants are effective for treating neuropathic pain, with their analgesic effects being independent of their antidepressant properties, particularly favoring those with noradrenergic activity.

Both first and second-generation antiepileptic drugs are effective for neuropathic pain, with second-generation drugs like gabapentin and pregabalin being safer for elderly patients, while tricyclic antidepressants are the most cost-effective option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressants and antiepileptic drugs for chronic non-cancer pain. Maizels, M., McCarberg, B.[2005]

A systematic review of 23 trials involving 1,074 patients found that anticonvulsants like carbamazepine and gabapentin can be effective for chronic neuropathic pain, particularly in conditions like trigeminal neuralgia and diabetic neuropathy, with numbers-needed-to-treat (NNT) values indicating moderate effectiveness.

However, the review also highlighted that there is limited evidence supporting the use of anticonvulsants for acute pain management, and they should be considered only after other treatment options have been explored for chronic pain syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticonvulsant drugs for acute and chronic pain. Wiffen, P., Collins, S., McQuay, H., et al.[2022]

A systematic review of 23 trials involving 1074 patients found that anticonvulsants like carbamazepine and gabapentin are effective for chronic neuropathic pain, particularly in conditions like trigeminal neuralgia and diabetic neuropathy, with numbers-needed-to-treat (NNT) values indicating moderate effectiveness.

However, the review concluded that there is insufficient evidence to support the use of anticonvulsants for acute pain management, and they should only be considered after other treatments have been tried for chronic pain syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WITHDRAWN. Anticonvulsant drugs for acute and chronic pain. Wiffen, PJ., Collins, S., McQuay, HJ., et al.[2022]

Antidepressants and anticonvulsants are effective treatments for neuropathic pain and chronic headache, providing alternatives to opioids for managing chronic pain conditions.

In addition to pain relief, antidepressants help alleviate associated issues like sleep disturbances, depression, and anxiety, which are common in patients suffering from chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant and anticonvulsant medication for chronic pain. Sullivan, MD., Robinson, JP.[2006]

In a study using a chronic pain model with male rats, both zonisamide and pregabalin showed significant efficacy in alleviating neuropathic pain, suggesting they could be effective alternatives to traditional pain medications.

The results indicate that anticonvulsants targeting N-type calcium channels or a combination of voltage-gated sodium and T-type calcium channels provide better pain relief compared to those that only inhibit T-type calcium channels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats. Goyal, S., Singla, S., Kumar, D., et al.[2020]

Newer generation anticonvulsants like gabapentin, tricyclic antidepressants (TCAs), and opioids are preferred therapies for treating neuropathic pain, but some patients may still experience pain despite these treatments.

For patients who do not respond to or cannot tolerate these first-line therapies, medications like venlafaxine or duloxetine may provide relief, although there are no direct comparisons between non-tricyclic options for neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nontricyclic antidepressants for neuropathic pain #187. Hawley, P.[2022]

Anticonvulsant drugs, particularly gabapentin, have shown significant efficacy in treating neuropathic pain conditions like painful diabetic neuropathy and postherpetic neuralgia, as evidenced by various clinical trials.

The emergence of newer anticonvulsants, such as pregabalin, suggests a promising future for their use in managing neuropathic pain, although further research is needed to fully understand their mechanisms and optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of anticonvulsants drugs for neuropathic painful conditions. Hussain, AM., Afshan, G.[2009]

Gabapentin is effective in providing pain relief for about one-third of adults with chronic neuropathic pain, with a number needed to treat (NNT) of 5.8 for moderate benefit and 6.8 for substantial benefit, based on a review of 29 studies involving 3571 participants.

While gabapentin is effective, it is associated with a high incidence of adverse events (66% of users), including dizziness (21%) and somnolence (16%), although serious adverse events were not more common than with placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Moore, RA., Wiffen, PJ., Derry, S., et al.[2022]

Gabapentin and pregabalin are the only antiepileptic drugs with reasonably good evidence supporting their efficacy in treating certain types of neuropathic pain, such as painful diabetic neuropathy and postherpetic neuralgia, with a notable reduction in pain intensity for some patients.

Despite the potential benefits of gabapentin and pregabalin, the overall response rate for achieving significant pain relief (at least 50% reduction) is low, and treatment is associated with a high risk of adverse events, highlighting the need for careful patient selection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Wiffen, PJ., Derry, S., Moore, RA., et al.[2023]

Gabapentin has been shown to be effective in managing chronic neuropathic pain, with a number needed to treat (NNT) of 4.3, meaning that about 4 patients need to be treated for one to experience significant pain relief.

In contrast, gabapentin did not demonstrate any benefit for acute pain management, indicating its effectiveness is primarily in chronic conditions like diabetic neuropathy and post-herpetic neuralgia, where the NNTs were even lower at 2.9 and 3.9, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WITHDRAWN: Gabapentin for acute and chronic pain. Wiffen, PJ., McQuay, HJ., Edwards, J., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6353204/

Pregabalin for neuropathic pain in adults - PMC Primary outcomes were: at least 30% pain intensity reduction over baseline; much or very much improved on the Patient Global Impression of Change (PGIC) Scale ( ...

2. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2024.1513597/full

Pregabalin vs. gabapentin in the treatment of neuropathic ... Pregabalin demonstrated significant improvement in pain assessed using the VAS scale and in functionality measured by the SF-12/SF-36 and EQ-5D.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1526590010007443

Systematic Review of the Comparative Effectiveness ... Both drugs reduced mean pain scores more than placebo at a modest rate (pregabalin, 38% to 50%; gabapentin, 51%). In a 6-month trial of pregabalin responders, ...

4. pfizer.com pfizer.com/news/press-release/press-release-detail/top_line_data_show_lyrica_met_primary_endpoint_in_clinical_trial_as_adjunctive_therapy_versus_levetiracetam_in_patients_with_partial_onset_seizures

Top-Line Data Show Lyrica Met Primary Endpoint in ... The top-line results indicate that the study met its primary endpoint by demonstrating that a comparable proportion of patients on Lyrica ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6469538/

Antiepileptic drugs for neuropathic pain and fibromyalgia We found that only for gabapentin and pregabalin was there some evidence that they worked in long‐term nerve pain with diabetes (painful diabetic neuropathy) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4110876/

Pregabalin: latest safety evidence and clinical implications for ... Flexible dosing of PGB at 150–600 mg/day provided greater responders (48% versus 34%), better tolerability and fewer dropouts due to AEs than with amitriptyline ...

7. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/l/Lyricacaps.pdf

DATA SHEET The safety and effectiveness of pregabalin has not been established in patients below the age of 18 years, with either epilepsy or neuropathic pain. Page 4 ...