Baclofen is a drug that was originally synthesized in the early 1960s by Heinrich Keberle, a Swiss chemist employed by the pharmaceutical company Ciba-Geigy. At the time of its synthesis, Keberle hypothesized that baclofen would prove effective as an antiepileptic agent, however, clinical trials yielded unfavorable results. Though ineffective as an antiepileptic, researchers noticed that baclofen decreased spasticity – a feature of abnormal skeletal muscle performance characterized by paralysis, increased tendon reflex, and muscle tension.
As a result of its preliminarily observed antispastic effect, researchers conducted trials to test the efficacy of baclofen for the attenuation of spasticity. Results of these trials supported its antispastic efficacy and safety, ultimately leading to the FDA approval of baclofen in 1977 for the treatment of spasticity associated with neurological conditions such as multiple sclerosis and spinal cord injuries. Although not approved to treat medical conditions other than spasticity, baclofen is occasionally prescribed off-label to help patients cope with opiate withdrawal.
When considering its mechanism of action as a GABA(B) agonist, it’s reasonable to hypothesize that baclofen might substantially reduce the severity of opiate withdrawal symptoms such as anxiety, headaches, muscle tension, pain, and restlessness. Furthermore, anecdotal accounts from individuals undergoing opiate withdrawal commonly report deriving significant therapeutic benefit from baclofen. That said, due to an overall lack of investigating the usefulness of baclofen during opiate withdrawal, it remains controversial as to whether its usage is justified.
How Baclofen May Help with Opiate Withdrawal: Managing Symptoms
The most obvious way in which baclofen is likely to prove helpful during opiate discontinuation is by reducing the severity of withdrawal symptoms. Reducing the severity of opiate discontinuation symptoms makes it easier for those who are struggling with opiate dependence to cope with the onslaught of disconcerting symptoms that emerge when they stop using. For example, baclofen may help a person manage anxiety, broken sleep, depression, muscle pains, and restlessness that occur during opiate detoxification.
That said, the significance of therapeutic benefit that you derive from baclofen will be largely subject to individual variation. Individual differences in responses to baclofen are likely contingent upon variables such as: dosing, frequency of administration, whether utilized as a standalone or along with other substances (e.g. medications, supplements, etc.), and genetics. A subset of individuals may find baclofen to be extremely effective for the management of their discontinuation symptoms, whereas others won’t report much of any benefit.
It should also be stated that baclofen might be equally helpful for two different individuals, yet in completely individualized ways. For example, one person may find that baclofen helps mostly with muscle spasms and restlessness, whereas another may rely on baclofen to help get a good night’s sleep. In any regard, below are list of opiate withdrawal symptoms that baclofen might help manage.
- Anxiety: Sometimes the anxiety that emerges during opiate discontinuation is so severe, that the person who initially decided to quit his/her opiates ends up reinstating them or resorts to illicit drugs just to avoid feeling anxious. Although some may attempt to fight through the anxiety, it’s easier said than done – especially for those with preexisting anxiety disorders. One way in which baclofen might help some individuals during opiate withdrawal is by reducing the intensity of their anxious symptoms. Baclofen interacts with the neurotransmission of GABA as a GABA(B) receptor agonist, whereby it induces an inhibitory effect to promote relaxation – ultimately making anxiety more manageable.
- Agitation: Another symptom that baclofen might reduce during opiate discontinuation is agitation. Agitation is characterized as a state of internal nervousness or excitement, often making it difficult to sit still and relax. What’s tough about opiate withdrawal is that during the early stages of quitting, you may feel extremely fatigued, yet simultaneously agitated as if your stomach is still churning with pent up energy. The administration of baclofen decreases excitatory neurotransmission in your brain and helps your body relax, possibly alleviating some of your agitation.
- Anger: Many individuals report experiencing explosive bouts of anger during opiate detoxification. This anger may interfere with social relationships at work and/or interactions with family members. In fact, the anger can become so severe that a person might feel the urge to punch, kick, claw, or smash something. It is well-understood that anger is generally related to neurochemical imbalances that occur when a potent opiate is discontinued after regular usage. Fortunately, baclofen can sometimes help decrease the intensity of the anger through the promotion of relaxation.
- Cravings: Anyone that’s used opiates frequently over a long-term is likely to experience opiate cravings during the detoxification process. These cravings may be powerful and extremely difficult to resist, especially if you have a source from which you can attain more opiates. Randomized controlled trials noted slight trends towards fewer cravings among baclofen users during detoxification compared to a placebo, however, the differences in cravings weren’t statistically significant. That said, many anecdotal accounts claim that baclofen during opiate withdrawal completely eliminates cravings.
- Depression: There’s some evidence to suggest that baclofen may help with the surfacing of depression during opiate withdrawal. A randomized controlled trial with 40 opiate-dependent participants used the Hamilton Depression Rating Scale (HAM-D) to assess mood during detoxification. It was documented that the patients receiving baclofen during detoxification experienced significantly fewer depressive symptoms than those receiving a placebo. Based on this finding, it’s reasonable to speculate that baclofen could make it easier to cope with detoxification-related depression.
- Fever: Certain people will experience major fluctuations in body temperature during opiate detoxification, all of which are usually accompanied by chills and sweats. In many cases, individuals notice that they develop a low-grade [or possibly a high] fever. To manage the fever, most will resort to using over-the-counter medications such as acetaminophen or NSAIDs. Interestingly, the action of baclofen as a GABA(B) receptor agonist decreases body temperature through a hypothermic effect. Although the temperature decrease may not be huge, it may help slightly with a fever during opiate detox.
- Headaches: Several preliminary studies indicate that baclofen may be effective as a treatment for various types of headaches including: cluster, migraines, and tension-type. Coincidentally, it is very common for individuals to experience headaches during opiate withdrawal. Considering the evidence supportive of the idea that baclofen treats various types of headaches, it’s reasonable to suspect that it might reduce the frequency and/or severity of headaches that emerge during opiate discontinuation.
- Insomnia: Insomnia, loosely defined as the inability to fall asleep at night and/or stay asleep throughout the night, commonly emerges during opiate detoxification. As a GABA(B) receptor agonist, baclofen is capable of inducing a sedative hypnotic effect that reduces the likelihood of insomnia for certain individuals. Furthermore, many baclofen users report that the drug makes them sleepy, and for this reason, they administer it in the afternoon or evening to override opiate discontinuation-related insomnia. Moreover, medical case reports of patients undergoing detox from inhalants and alcohol support the idea that baclofen can treat insomnia during substance withdrawal.
- Irritability: In the early weeks of detoxification from opiates, many individuals experience heightened irritability. Irritability that occurs during opiate detox can be so overwhelming that even casual conversations with friends, family, and co-workers – are perceived as annoying or downright infuriating. When irritability is left unmanaged, it can lead some individuals to take their internal frustrations out on others via verbal and/or physical abuse. One strategy for managing irritability may involve utilizing pharmacological interventions, including baclofen. As an agonist of GABA(B) receptors, baclofen increases feelings of calmness and relaxation, possibly decreasing the intensity of irritability during opiate withdrawal.
- Mood swings: During opiate detoxification, many experience unpredictable [and possibly unmanageable] mood swings. Mood swings occurring during opiate detoxification are largely due to neurochemical disarray within the brain. As a result, one minute a person may feel angry, the next minute depressed and/or various permutations of negative emotion (e.g. anxious/depressed, depressed/angry, etc.). Though mood swings during detoxification are considered normal, they may significantly impair a person’s decision making and/or quality of life. Baclofen is sometimes capable of reducing negative mood swings and/or emotional upheavals that occur during opiate withdrawal.
- Muscle spasms: It is known that baclofen exerts a strong antispastic effect, hence the reason it’s approved by the FDA for the treatment of muscle spasms among persons with neurological and/or spinal conditions. There’s reason to think that the antispastic effect may also be useful for individuals dealing with unremitting muscle spasms in opiate withdrawal. Muscle spasms occurring during opiate withdrawal can be distracting, anxiety-provoking, and sometimes painful. Anyone taking baclofen during opiate detox may be surprised to find that it totally prevents and/or reduces the intensity of these spasms.
- Pain: Body aches and muscle pains are ordinary symptoms of opiate withdrawal. With long-term opiate usage, various receptor sites plus downstream feedback loops adjust to the effect of opiates and the brain’s ability to manufacture and/or respond to endorphins is thought to decrease. As a result, when a person stops using his/her opiates, intense pain may emerge throughout the body due to the neurochemical and hormonal adaptions that occurred while a person was using opiates. Since research supports the idea that baclofen can effectively reduce various types of pain, it’s reasonable to think that it could help with body aches and muscle pains during opiate withdrawal.
- Restlessness: Anyone committed to detoxification from opiates after an extended period of regular administration is likely to experience some restlessness. Many former opiate users report specifically experiencing restless leg syndrome (RLS), but restlessness sensations can also occur in the upper body as well (e.g. arms). Without pharmacological support, restlessness may seem impossible to manage. Administration of baclofen during opiate withdrawal should relax muscles enough to decrease some of the restlessness that occurs.
- Sleep: Although sleep disturbances are considered normal during opiate withdrawal, they may significantly impair sleep quality and/or quantity. Any impairments in sleep quality and/or quantity could prolong the detoxification process and exacerbate debilitating withdrawal symptoms. For this reason, it’s critical that anyone undergoing opiate detox makes a concerted effort to get a good night’s sleep. Strategic usage of baclofen may effectively enhance sleep indirectly by reducing detox-related symptoms such as insomnia, restlessness, spasms, and anxiety – all of which can detrimentally affect sleep.
- Tension: Discontinuation of opiates after an extended term of usage can trigger prolonged or acute episodes of increased muscle tension, often accompanied by aches and pains. Using baclofen during opiate detoxification should help some individuals cope with any uncomfortable increase in muscle tension. Since baclofen induces a muscle relaxant effect via its agonism of GABA(B) receptors, it should be nearly impossible for muscles to remain tense during discontinuation.
- Tremor: Experiencing the shakes or “tremor” during opiate detoxification is relatively normal, however, it can be disconcerting. Many individuals are extremely self-conscious of tremor, and in some cases, they may report that tremor interferes with their coordination and/or motor skills. Nobody wants to experience tremor or shakiness, especially in an academic or occupational setting. A possibly efficacious way to minimize the tremors during opiate discontinuation is via the administration of baclofen. Baclofen relaxes the muscles and has been used with success to ameliorate tremor.
- Twitching: Another symptom that’s similar to muscle spasms and tremor that people may report during opiate detox is twitching. The twitching that occurs from discontinuation of opiates can be extremely distracting and annoying. That said, most people can cope with a bit of twitching. While taking baclofen, some individuals will notice that their opiate withdrawal-related twitching decreases or is totally eliminated.
How Baclofen Works (Mechanism of Action)
Though baclofen was engineered in the 1960s and FDA approved in the late 1970s, nobody fully understood its pharmacodynamics until the 1980s. Years after its synthesis, a professor named Norman Bowery identified the GABA(B) receptor site upon which baclofen acted. It is now understood that activation of the GABA(B) receptor stimulates the opening of potassium (K+) channels, which in turn, hyperpolarizes neurons.
Hyperpolarization of neurons inhibits voltage-gated sodium (Na+) channels and corresponding neuronal action potentials. As a result of baclofen’s action as a GABA(B) agonist, CNS activity is suppressed and opiate detoxification symptoms become easier to manage. Other possible mechanisms of baclofen that might contribute slightly to its overall therapeutic effect during opiate detoxification include: modulation of mesolimbic dopaminergic activity and blockade of voltage-gated calcium (Ca+) channels.
GABA(B) receptor agonist: Baclofen functions chiefly as an agonist at the B-subunit of GABA (gamma-aminobutyric-acid) receptors, affecting both the presynaptic and postsynaptic receptor sites. Presynaptic agonism decreases calcium currents to inhibit release of excitatory amino acids, whereas postsynaptic agonism increases potassium currents to hyperpolarize neurons. The net effect is that excitatory neurotransmission is reduced, thereby facilitating myorelaxation, psychological sedation, and hypothermia.
It is important to emphasize that GABA(B) receptors differ from GABA(A) and GABA(C) subtypes in that they are metabotropic receptors (membrane receptors that act through secondary messengers). Research indicates that GABA(B) receptors are densest within the limbic system, an area of the brain implicated in control of basic emotions (anger, fear, pleasure) and drives (dominance, hunger, sex). Due to the location of GABA(B) receptors in the limbic system, many postulate that their activation with baclofen could improve emotional regulation and attenuate anxiety.
This may explain why some individuals notice that taking baclofen reduces mood swings and anxiety during opiate withdrawal. Furthermore, it should be mentioned that GABA(B) receptors are of proximal location to mesolimbic dopaminergic neurons, and as a result, when GABA(B) receptors are agonized, mesolimbic dopamine secretion is reduced. Some hypothesize that decreasing mesolimbic dopamine secretion is likely to minimize cravings for opiates during detoxification in a subset of baclofen users.
Moreover, the action of baclofen upon GABA(B) receptors may be capable of attenuating body aches and/or muscle pains that occur during opiate withdrawal. Case reports suggest that a subset of patients with varying types of pain derive benefit from baclofen’s GABA(B) agonism to help with pain management. Preliminary research suggests that GABA(B) agonism can generate an antinociceptive response, thereby blocking the sensory detection of pain.
Calcium (Ca+) channel blocker: To a markedly lesser extent than its action upon GABA(B) receptors, baclofen appears to block the alpha-2-delta subunit of voltage-gated calcium (Ca+) channels. When administered at low doses, baclofen’s blockade of voltage-gated calcium channels is thought to be insufficient enough for the generation of a therapeutic effect. However, when administered at higher doses, baclofen’s blockade of voltage-gated calcium channels may provide a modest therapeutic effect to attenuate various symptoms of opiate detoxification.
Most research suggests that the blockade of alpha-2-delta subunits of voltage-gated calcium channels yields an antinociceptive effect. This antinociceptive effect is generally therapeutic for individuals with diagnoses of neuropathic pain, but may also reduce other types of pain. Given the fact that blockade of alpha-2-delta subunits of voltage-gated calcium channels can induce an antinociceptive effect, it’s plausible that individuals taking high-dose baclofen might experience less pain during opiate withdrawal.
Benefits of Using Baclofen for Opiate Withdrawal (Possibilities)
There are numerous potential benefits associated with using baclofen during opiate detoxification. The most obvious benefit to be attained from administration of baclofen during opiate detox is that it may substantially attenuate the severity of discontinuation symptoms, thereby making it easier for patients to completely detoxify. Other favorable aspects of utilizing baclofen during opiate withdrawal include its: adjunct efficacy, low abuse potential, monotherapeutic efficacy, low cost, and tolerability.
- Abuse potential: Unlike most drugs that modulate the activation of GABA receptors (e.g. benzodiazepines) to exert a therapeutic effect, baclofen has a very low abuse potential. Its low abuse potential stems from the fact that baclofen agonizes the GABA(B) receptor without affecting the GHB receptor. Moreover, baclofen’s agonism of GABA(B) receptors is thought to inhibit dopamine secretion in the mesolimbic pathway, ultimately negating cravings and/or reward associated with its usage. There are no reports of baclofen abuse (outside of suicide attempts) nor addiction in the medical literature.
- Adjunct option: In many cases, individuals undergoing opiate detoxification derive inadequate symptomatic reduction from monotherapeutic interventions. Although baclofen appears safe and effective as a monotherapy among those undergoing opiate detox, it also appears relatively safe and effective when administered along with other medications. One trial discovered that the administration of baclofen with either clonidine or lofexidine – plus oxazepam, ketoprofene, naloxone, and naltrexone – effectively managed opiate withdrawal symptoms without safety or tolerability issues. Additionally, it’s reasonable to suspect that the administration of baclofen along with other medications could yield a synergistic effect whereby therapeutic value is substantially greater than each agent as a standalone.
- As-needed: Many medications such as antidepressants need to be administered on a daily basis without skipping a day to deliver therapeutic effects. In some cases, even baclofen is recommended to be taken several times per day, on a daily basis to maintain therapeutic effects. That said, some individuals report successfully using baclofen on an “as-needed” basis such that they only administer it when symptoms become most severe. The “as-needed” possibility of administration with baclofen may be preferred by some patients who want to avoid feeling under the influence of a pharmaceutical drug around-the-clock.
- Evidence-based: Although baclofen is neither FDA approved nor medically recommended for the management of opiate detoxification symptoms, mounting evidence supports its therapeutic value among patients during opiate detoxification. As of current, there are two moderately-sized randomized controlled trials in which baclofen was found to be effective for the management of opiate withdrawal symptoms. Specifically, one trial discovered that baclofen was superior to clonidine in attenuating certain aspects of opiate detox (e.g. psychological symptoms) and the other noted that baclofen was significantly more effective than a placebo. Most patients who use baclofen for opiate detox like the fact that it’s evidence-based.
- Few interactions: Compared to most pharmaceutical medications, baclofen is associated with a low risk of pharmacokinetic interactions. The low risk of pharmacokinetic interactions is due to the fact that baclofen is not subject to hepatic metabolism and undergoes minimal biotransformation prior to excretion. In other words, baclofen shouldn’t expedite or prolong the speed at which co-administered substances are metabolized nor their corresponding duration of effect. The only major interactions that could occur are associated with pharmacodynamics such that suppression of CNS activity may be extreme.
- Low cost: Due to the fact that patents for baclofen have long expired, it’s now manufactured as a generic and can be attained at an extremely low cost. The low cost of baclofen may be preferable for individuals who cannot afford the newest brand name medications to help ease opiate withdrawal symptoms. Newer brand name prescription drugs that are still under patent often cost patients hundreds of dollars for a monthly supply, and without good health insurance, most of this is financed out-of-pocket. Comparatively, around 90 pills of 10 mg baclofen retail within the price range of $10 to $20 at most pharmacies. Even if you were to pay the highest possible price of $20 for 90 pills at 10 mg, this equates to roughly $0.22 per pill – a price most can afford.
- Slow tolerance onset: Some GABAergic drugs like benzodiazepines which allosterically modulate GABA(A) receptors are associated with rapid onset of tolerance. In other words, within weeks of regular usage, their therapeutic effects wear off. Baclofen is distinct from other GABAergic medications in that it is not associated with rapid tolerance induction. Medical reports suggest that its antispastic effects can be maintained even after years of continuous usage. Although tolerance to baclofen will occur over a long-term with regular usage, the tolerance is thought to be slower than similar medications due to its lack of a hepatic metabolism and selective action upon GABA(B) receptors.
- Superior to clonidine (?): One randomized controlled trial in which baclofen was compared to clonidine discovered that both drugs were of equal efficacy in alleviating physical symptoms of opiate detoxification. That said, baclofen was significantly more effective than clonidine in alleviating psychological symptoms of opiate detoxification. Additionally, when side effects were compared, users of clonidine experienced significantly higher rates of hypotension. Based on these findings, some might perceive baclofen as being more effective and safer than clonidine in the management of outpatient detox.
- Tolerability: In opiate withdrawal, baclofen is regarded as being extremely tolerable. One randomized controlled trial reported that baclofen was as tolerable as clonidine, and another reported that it was of comparable tolerability to a placebo. In other words, a majority of persons undergoing treatment with baclofen won’t discontinue treatment due to adverse reactions nor unwanted side effects.
Drawbacks of Using Baclofen for Opiate Withdrawal (Possibilities)
There may be some drawbacks associated with using baclofen for opiate withdrawal that are worth mentioning. Perhaps the most significant drawback is that baclofen may be unable to adequately reduce opiate detoxification symptoms, whereby the user still has a difficult time completing detox. Additionally, some individuals may experience adverse reactions, unwanted side effects, or interactions while taking baclofen. Other drawbacks to consider before using baclofen to manage opiate detoxification symptoms include: its off-label status, potentially deleterious long-term effects, and/or withdrawal symptoms.
- Adverse reactions: Though relatively uncommon, certain people may be unable to tolerate baclofen. In rare cases, baclofen may cause an allergic reaction, accompanied by difficulty breathing, fever, a skin rash, sweating, swelling of limbs, and/or vomiting. Other adverse reactions that may occur while using baclofen include: severe confusion, hallucinations, and/or depression. Obviously if you were to experience adverse reactions from baclofen, it may add to the burden of opiate detoxification.
- Cognitive deficits: As an agonist of the GABA(B) receptor, baclofen can be sedating, possibly to the extent that the sedation interferes with normative cognitive capabilities. During treatment with baclofen, you may feel as though you’re unable to think clearly, learn and/or retain information, retrieve memories, organize your thoughts, and/or plan for the future. This is because when arousal plummets too low, cognition becomes impaired. Many will also report experiencing “brain fog” such that thoughts seem clouded or hazy.
- Contraindications: It is possible you might have a medical condition with which baclofen is contraindicated. Examples of medical conditions that could be contraindicated with baclofen include: epilepsy, renal dysfunction, schizophrenia, and stroke. Baclofen is also said to be contraindicated during pregnancy and/or nursing due to the fact that it may respectively interfere with fetal and newborn development. Although baclofen’s contraindications are limited, they might prevent a subset of individuals from safely using it.
- Impaired motor skills: Any drug that suppresses CNS activity, induces sedation, and myorelaxation – may substantially impair motor skills. Impaired motor skills compromise your ability to safely operate motor vehicles and/or heavy machinery. Anyone who continues operating vehicles and/or machinery while taking baclofen may be endangering their own life, as well as lives of others. If for whatever reason you need to drive and/or use machinery during your detox, you may be unfit to receive baclofen.
- Ineffective: Although there are multiple randomized controlled trials suggesting that baclofen provides substantial therapeutic benefit during opiate withdrawal, neither of these trials implemented large sample sizes. Lacking large sample sizes makes it difficult to confidently suggest that baclofen is a therapeutically useful first-line intervention for a majority of persons undergoing opiate withdrawal. It’s possible that a future large-scale trial might conclude that baclofen is no more effective than a placebo to manage opiate detox. Moreover, even if baclofen was medically-approved to help manage opiate discontinuation symptoms, due to individual variation in drug responses, a subset of patients may report deriving zero noticeable benefit from its administration.
- Interactions: While the odds of a pharmacokinetic interaction resulting from baclofen are low (largely due to nonexistent hepatic metabolism), baclofen can interact with other substances through potentiation of CNS suppression. Since baclofen decreases activity in the CNS to induce myorelaxation and sedation, it may be dangerous to administer baclofen with certain drugs that suppress the CNS. For example, substances like: alcohol, antihistamines, antihypertensive agents, barbiturates, benzodiazepines, muscle relaxants, and opioids – should be avoided while taking baclofen, as the combination may induce respiratory depression, possibly leading to death. Combining various neuropsychiatric drugs such as TCAs (tricyclic antidepressants) and MAOIs (monoamine oxidase inhibitors) may also cause weakness and low blood pressure, respectively. These interactions may limit one’s ability to safely take baclofen during opiate detoxification.
- Long-term effects: Baclofen is generally used transiently to help manage the most debilitating symptoms of opiate discontinuation, and once these symptoms subside, the baclofen is discontinued. Still, it’s possible that a subset of individuals might resort to using baclofen over a long-term to help with PAWS (Post Acute Withdrawal Syndrome) and/or to prevent relapse of opiate usage. Due to the fact that related GABAergic medications like benzodiazepines have been linked to dementia and serious memory deficits with long-term usage, it’s fair to speculate that deleterious cognitive and/or physiological effects could occur as a result of long-term baclofen administration. Research by Tang and Hasselmo (1996) notes that long-term administration of baclofen to rats impairs recognition memory. A study among humans that have been using baclofen for over 5 years documented a significant worsening in psychosocial aspects of perceived health status. In brief, assuming you were to take baclofen long after your opiate detoxification, it may induce unfavorable long-term effects.
- Off-label: Another disadvantage associated with using baclofen during opiate detoxification is that it’s an “off-label” intervention. In other words, baclofen is not formally endorsed by the FDA for the management of opiate detoxification symptoms. As a result of its “off label” status, not every doctor will prescribe baclofen to patients during opiate detox. Additionally, if you were to switch doctors midway through opiate detoxification, your new doctor may disagree with the decision to use baclofen, and as a result, you might end up on a different (potentially less effective) medication. Even if your doctor agrees to prescribe baclofen to help with your detox, due to its off-label administration, more frequent doctor visits may be needed to attain refills – which might be a hassle for some patients.
- Side effects: Though baclofen is generally well-tolerated at medically-prescribed dosages, it is not devoid of side effects. In some cases, the side effects may be difficult to manage and/or so extreme that a patient is unable to differentiate them from symptoms of opiate detoxification. Another possibility is that the side effects of baclofen might intensify certain symptoms of opiate detoxification. Among the most common side effects of baclofen include: drowsiness, dizziness, tiredness, headache, sleep disturbances, hypotension, confusion, nausea, frequent urination, urinary retention, weakness, and constipation. Some individuals may find these side effects to be unbearable and may prefer a different medication to help with their detox.
- Tolerance onset: While tolerance to baclofen is thought to be of slower onset than that of other GABAergic medications, anyone who uses baclofen regularly and/or for an extended duration will eventually become tolerant to its therapeutic effect. Many report that baclofen works extremely well in the early weeks and/or months of treatment, but after awhile, its therapeutic effect will diminish as a result of neuroadaptive changes (e.g. GABA(B) receptor upregulation). It is thought that tolerance to the psychological effects of baclofen occurs at a quicker pace than tolerance to its physical effects. In any regard, some patients may be disappointed with baclofen after tolerance sets in and they aren’t deriving the therapeutic benefit that they once were.
- Unknown long-term efficacy: There are often individualized differences in the severity of opiate detoxification symptoms, the duration of symptoms, and a person’s ability to cope with them. It is known that a subset of individuals will experience an acute stage of intense discontinuation symptoms, followed by a post-acute stage of lingering withdrawal symptoms. As a result, some individuals may continue taking baclofen over a longer-term to help manage the post-acute symptoms that remain. Since post-acute symptoms can remain for months, and in extreme cases, years, it’s possible that baclofen’s administration will continue. The long-term efficacy of baclofen for the management of opiate detoxification symptoms isn’t elucidated. It’s possible that baclofen may stop providing a therapeutic effect sooner than expected.
- Withdrawal symptoms: While baclofen can help with opiate detoxification, some individuals may not realize that baclofen has withdrawal symptoms of its own. If administered regularly, at high doses, for a long-term – discontinuation of baclofen will be challenging. Research suggests that withdrawal symptoms from baclofen are often as as severe as those associated with benzodiazepines and alcohol. Examples of withdrawal symptoms that might occur after stopping baclofen include: hallucinations, delusions, confusion, agitation, rebound anxiety, insomnia, dizziness, cognitive impairment, restlessness, seizures, hyperthermia, mania, itchiness, and tremor. Furthermore, abrupt (i.e. “cold turkey”) discontinuation of baclofen is considered dangerous.
Baclofen for Opiate Withdrawal (Review of Research)
To understand whether baclofen might be an effective medication for the management of opiate withdrawal symptoms, it is necessary to analyze trials in which baclofen was evaluated for this specific purpose. As of current, there are just 2 moderately-sized randomized controlled trials and 1 pilot study in which baclofen was assessed for the treatment of opiate discontinuation. Results from these trials indicate that baclofen appears safe, tolerable, and therapeutically useful as a pharmacological intervention among those undergoing opiate detox. That said, data from larger-scale randomized controlled trials is needed to confirm preliminary findings.
2003: Baclofen for maintenance treatment of opioid dependence: a randomized double-blind placebo-controlled clinical trial [ISRCTN32121581].
Several preclinical trials indicate that baclofen, a GABA(B) receptor agonist, appears helpful in the management of opiate dependence. For this reason, researchers Assadi, Radgoodarzi, and Ahmadi-Abhari (2003) organized a study to evaluate the therapeutic potential of baclofen as a treatment for opiate dependence. The study implemented a randomized, double-blinded, placebo controlled design and included 40 opioid-dependent patients.
All patients underwent detoxification from opioids and were randomly assigned to receive either: baclofen (60 mg/day) or a placebo – for a 12-week duration. The primary outcome measure was treatment adherence. Secondary outcome measures were also assessed including: opioid and alcohol usage (based on urinalysis results and self-reports), intensity of opioid cravings (measured with the visual analogue scale), opioid discontinuation syndrome (measured with the Short Opiate Withdrawal Scale) and depression (measured with the HAM-D).
Results indicated that treatment adherence was substantially greater among baclofen recipients compared to placebo recipients. Additionally, secondary measures revealed that baclofen was significantly more effective than the placebo in reducing symptoms of opiate discontinuation syndrome and depression. Although statistically insignificant, there were trends towards greater improvement among baclofen recipients on measures of cravings and self-reported substance (opioid and alcohol) usage – compared to the placebo recipients.
Furthermore, there were no significant differences in side effects observed in the baclofen and placebo groups, suggestive of the fact that baclofen is well-tolerated. Researchers concluded that further research is warranted to determine the efficacy of baclofen as a maintenance treatment among patients with opioid dependence. Nonetheless, this study supports the idea that baclofen is likely to provide some degree of benefit during detoxification from an opiate.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/14624703
2001: Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial.
It is understood that baclofen is effective as an intervention for spasticity, however, accumulating evidence suggests that it may also be an efficacious in the management of opiate discontinuation syndrome. For example, a randomized, doubled-blinded, controlled trial by by Ahmadi-Abhari, Akhondzadeh, Assadi, et al. concluded that baclofen appears as effective as clonidine in reducing physical symptoms of opiate discontinuation, and even more effective than clonidine in decreasing psychological symptoms. In this same trial, researchers recorded the side effects experienced by baclofen (up to 40 mg/day) and clonidine (up to 0.8 mg/day) users.
After the trial, researchers analyzed the side effect data and compared the tolerability of baclofen to that of clonidine. Results indicated that there were no significant differences in the severity of side effects nor dropouts (indicative of intolerability) among baclofen and clonidine recipients. Although the two drugs appeared to be of equal tolerability, it was reported that clonidine users experienced hypotension-related problems, whereas baclofen users did not.
Considering the increased incidence of hypotension-related problems among clonidine users, some might argue that baclofen is the slightly safer intervention of the two. Researchers concluded that baclofen could be a viable outpatient intervention to help manage symptoms of opiate cessation. Moreover, since baclofen may be slightly safer than clonidine and more effective for treating psychological symptoms of opiate discontinuation, perhaps it is an all-around superior intervention.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/11286609
2001: Lofexidine versus clonidine in rapid opiate detoxification.
Gerra, Zaimovic, Giusti, et al. (2001) conducted a study to compare the efficacy of lofexidine to clonidine for the management of rapid opiate detoxification symptoms. For the study, researchers recruited 40 individuals with heroin dependence, divided them into two groups of 20, and assigned them at random to receive one of two pharmacological regimens. The first regimen consisted of clonidine – plus oxazepam, baclofen, and ketoprofene, with naloxone and naltrexone for 3 days.
The second regimen consisted of lofexidine – plus oxazepam, baclofen, and ketoprofene with naloxone and naltrexone for 3 days. Participants underwent assessments that evaluated their discontinuation symptoms, cravings, and moods, and were also subject to toxicological urinalysis screenings. Results indicated that both pharmacological regimens were effective for the management of rapid opiate detoxification symptoms, however, recipients of lofexidine exhibited substantially fewer withdrawal symptoms, mood problems, sedation, and hypotension – compared to recipients of clonidine.
Between the two groups of 20 participants, there were no substantial differences in the intensity of cravings, urinary opiate metabolites, nor dropout rates. Researchers concluded that lofexidine appeared more effective than clonidine in a 3-day rapid opiate detoxification for the management of withdrawal symptoms, dysphoria, and mood – plus, because it didn’t cause hypotension, it was considered safer than clonidine. Although this study didn’t directly examine the efficacy of baclofen, it’s reasonable to consider that baclofen may have facilitated a substantial therapeutic effect in each of the pharmacological cocktails. Moreover, this study supports the idea that baclofen is safe and tolerable when administered as part of a multi-drug intervention for the management of opiate detoxification.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/11516922
2000: Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal.
Akhondzadeh, Ahmadi-Abhari, Assadi, et al. (2000) noted that many opiate detoxification strategies have been implemented for the management of opiate withdrawal symptoms. In the 1990s, alpha-adrenergic agonists appeared to be among the most popular interventions for opiate detoxification, however, the GABA(B) receptor agonist baclofen garnered some interest as a potentially-therapeutic option. For this reason, researchers organized a trial in which the efficacy of baclofen was assessed in managing opiate withdrawal symptoms.
A total of 62 individuals with opioid dependence (in accordance with DSM-IV criteria) were recruited to participate in a randomized, double-blinded, controlled trial. Participants were assigned at random to receive baclofen (40 mg/day maximum) or clonidine (0.8 mg/day in divided doses). To gauge the effectiveness of each intervention, researchers recorded the severity of patients’ opiate withdrawal symptoms over a 14-day duration by using the Short Opiate Withdrawal Scale (SOWS).
Results from the trial suggested that baclofen and clonidine were equally effective in reducing physical symptoms of opiate withdrawal. Yet by comparison, baclofen was substantially more effective than clonidine in the management of psychological symptoms of opiate withdrawal. It was concluded that baclofen could be a novel intervention for the management of opiate withdrawal symptoms.
Still, researchers acknowledged that a larger-scale trial is necessary to confirm these results. In addition to conducting a larger-scale trial, perhaps a long-term trial is warranted as well. It would help to know if findings would be similar after a 1-month or 3-month duration. Overall, this trial provides evidence to support the hypothesis that baclofen is useful during opiate withdrawal.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/11123486
1992: Baclofen-assisted detoxification from opiates. A pilot study.
A pilot study conducted by Krystal, McDougle, Kosten, et al. (1992) sought to determine the therapeutic value of baclofen during opiate detoxification. For the study, researchers recruited 5 patients with opiate dependence who had been receiving methadone maintenance therapy. Following the abrupt discontinuation of methadone, all patients received baclofen at dosages up to 80 mg/day.
Upon receiving baclofen, subjective reports by patients documented modest reduction in overall discomfort. That said, 3 of the 5 participants were unable to complete opiate detoxification with baclofen. This was primarily due to the fact that baclofen was incapable of managing severe headaches, muscle aches, and vomiting that occurred during their discontinuation of methadone.
Interestingly, the 3 participants who responded poorly to baclofen derived substantial benefit from clonidine, thereby enabling them to complete opiate detoxification. Researchers concluded that at dosages up to 80 mg/day, baclofen exhibits limited therapeutic potential as a primary intervention for opiate dependence. Nonetheless, it was acknowledged that baclofen might have therapeutic potential when administered as an adjunct during opiate detoxification.
It is important to note that there are some serious limitations associated with this pilot study including its small sample size and lack of a randomized controlled design. Furthermore, it is possible that the dosage of 80 mg/day may have been too low to control opiate discontinuation symptoms. Not much can be concluded from this trial other than baclofen appeared effective in 2 patients and ineffective in 3 patients from a 5-person sample undergoing opiate detox.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/1324986
Limitations in the Research of Baclofen for Opiate Withdrawal
There are several limitations associated with the research of baclofen for opiate withdrawal. Arguably the biggest limitation is that there are zero large-scale randomized controlled trials that followed-up on preliminary findings suggestive of the fact that baclofen may be therapeutically useful as an intervention during opioid discontinuation. Other obvious limitations with the research of baclofen include: its lack of testing as an adjunct (rather than a monotherapy), trial duration, and the fact that most of the trials have been conducted by similar researchers.
- Few trials: The single biggest limitation of the research is that just 3 trials have been conducted in which the efficacy of baclofen for the treatment of opiate discontinuation syndrome was explored. Just 2 of these 3 trials implemented randomized controlled designs, whereas the other trial was non-randomized and uncontrolled. Despite promising results in the 2 robustly-designed trials, no follow-up studies have been conducted. A greater number of trials, assuming they are randomized and controlled, can provide more data to help elucidate the usefulness of baclofen during opiate cessation.
- Incentive: Since the patent for baclofen has long-expired and the drug is manufactured as a generic, pharmaceutical companies aren’t financially-incentivized to continue investigations of baclofen’s therapeutic value during opiate withdrawal. Although it would be useful for many to have definitive data regarding baclofen’s safety and efficacy in the management of opiate discontinuation syndrome, no one will fund the research. Researchers don’t generally have the funding nor the time to conduct large-scale trials to determine whether an older drug like baclofen may treat a condition for which it was never approved. Most current research involves testing newer, patented chemicals with the potential for a massive financial return on investment.
- Monotherapy-only: A majority of individuals who use baclofen during opiate discontinuation do not administer baclofen as a monotherapy, instead, they use it along with a host of other substances (medications and supplements). For this reason, another limitation associated with the research is that zero studies have specifically investigated the efficacy of adjunct baclofen to other medications for the management of opiate discontinuation syndrome. One study comparing lofexidine to clonidine along with baclofen (and several other medications) documented that each combination was safe and tolerable, suggesting that baclofen can be administered as an adjunct. Still, more research needs to be done to determine which medications baclofen works best with and/or the dosages at which adjunct baclofen is safe plus effective.
- Researchers: Currently, each of the randomized controlled trials assessing the efficacy of baclofen for the management of opiate discontinuation syndrome were conducted by the several of the same researchers. An analysis of study authors indicates that Ahmadi-Abhari and Assadi conducted a study published in 2003 and another published in 2000. Although researcher homogeneity isn’t always problematic, it may increase risk of bias and/or inaccurate results. For this reason, greater researcher heterogeneity may be needed.
- Sample sizes: Of the 3 available trials that tested baclofen among patients undergoing opiate detox, the sample sizes were not large enough to generate high-quality data. The smallest trial (non-randomized/uncontrolled) tested baclofen in an extremely small group of just 5 patients. Two moderately-sized trials (randomized/controlled) tested baclofen in respective groups of 62 patients and 40 patients. To accurately know whether baclofen is an effective intervention among those undergoing opiate detoxification, larger [randomized controlled] trials are needed with hundreds of participants.
- Trial duration: One randomized controlled trial compared the efficacy of baclofen to a placebo for the treatment of opioid dependence over a 12-week duration, however, other randomized controlled trial was conducted over a 2-week duration. Knowing that many patients experience PAWS (Post Acute Withdrawal Syndrome), more long-term trials similar to the 12-week one are needed. Longer-term trials will help us understand whether baclofen continues to facilitate a therapeutic effect when administered over a longer term.
Verdict: Baclofen likely useful for the management of opiate withdrawal symptoms
At this time, more quality evidence is needed suggesting that baclofen is safe and effective for the management of opiate detoxification before baclofen can be regularly prescribed for this purpose. As was discussed above, the research of baclofen in the management of opiate withdrawal is limited by the fact that no large-scale randomized controlled trials have been conducted. The first trial in which baclofen was evaluated during opiate detoxification was a 5-patient pilot study conducted by Krystal, McDougle, Kosten, et al. (1992).
Results from this pilot study did not support the efficacy of baclofen during opiate detoxification. Only 2 of 5 patients completed detoxification with baclofen, whereas the remaining 3 patients noted that baclofen was incapable of managing detoxification-related headaches, muscle aches, and vomiting. Additionally, when the 3 patients who were unable to tolerate baclofen transitioned to receiving clonidine, they derived significant symptomatic relief and completed detoxification – indicating that clonidine may be a superior drug for detox.
That said, the data generated by this small-scale pilot study was of extremely poor quality. Thereafter, a better designed double-blind RCT by Ahmadi-Abhari, Akhondzadeh, Assadi, et al. (2000) compared the efficacy of baclofen to clonidine during opiate detox among 62 patients with opioid dependence over a 2-week duration. The trial outcome indicated that both drugs were equally effective in managing physical symptoms of withdrawal, but baclofen was superior in managing psychological symptoms.
What’s more, a comparative analysis of side effects associated with baclofen and clonidine suggested that baclofen is likely a safer drug for outpatient usage during opiate detox due to lower rates of hypotension. Considering baclofen’s greater efficacy in managing psychological symptoms of withdrawal and lower odds of inducing hypotension, it’s reasonable to suspect that it may be a superior intervention to clonidine for during opiate detoxification. More quality data supporting the therapeutic value of baclofen during opiate detox were derived from a RCT by Assadi, Radgoodarzi, and Ahmadi-Abhari (2003) in which baclofen was compared to a placebo over a 12-week duration.
Recipients of baclofen exhibited greater adherence to treatment and fewer unwanted symptoms associated with opiate detoxification – compared to recipients of the placebo. Additionally, side effects did not differ among baclofen and placebo recipients, indicating that baclofen is well-tolerated. Findings from the aforestated randomized controlled trials in which baclofen’s efficacy was respectively compared to clonidine and a placebo for the management of opiate detoxification symptoms support the hypothesis that it is a therapeutically valuable monotherapy during detox.
Nevertheless, due to significant individual variation in the severity of detoxification symptoms and responses to baclofen, not everyone will derive adequate therapeutic benefit from baclofen monotherapy. In extreme cases, patients undergoing opiate detox may require a multi-drug intervention to help curb detoxification symptoms. A trial by Gerra, Zaimovic, Giusti, et al. (2001) revealed that baclofen is safe and effective for the management of opiate detox symptoms when administered along with other medications including: clonidine or lofexidine – plus oxazepam, baclofen, and ketoprofene, with naloxone and naltrexone.
Moreover, baclofen isn’t subject to hepatic metabolism, making it extremely unlikely to pharmacokinetically interact with other medications. In summary, there’s evidence from multiple mid-sized RCTs to support the safety and therapeutic efficacy of baclofen in the management of opiate withdrawal symptoms, regardless of whether administered as a monotherapy or adjunct. Overall, it’s reasonable to believe that baclofen will provide substantial therapeutic benefit for a subset of patients undergoing opiate detoxification.
How to use Baclofen for opiate withdrawal…
If you’re going to take baclofen for opiate withdrawal symptom management, it is important to work closely with a medical professional. Medical professionals will help ensure that baclofen is safe to take in accordance with your current health status and medication regimen. The goal is to administer the lowest possible dose of baclofen necessary to help you get through the opiate detoxification process. Once the detoxification process is complete, the baclofen can be gradually tapered and discontinued.
- Consult a medical professional: The first step anyone should take prior to undergoing opiate detoxification involves consulting a medical professional, preferably a skilled/empathetic psychiatrist with experience in opiate detoxification. A psychiatrist will be able to accurately determine whether you are a good fit for receiving baclofen during the detoxification process. Those who fail to consult a medical professional and attain baclofen illicitly may not realize that its administration might be unsafe in conjunction with other substances that they use and/or health conditions that they have. A medical professional is equipped to determine which medications might work best for you as an individual. It may turn out that other medications are safer and/or more effective than baclofen to help you get through detox.
- Work closely with your doctor: In the event that your doctor prescribes baclofen to mitigate opiate detoxification symptoms, it is recommended to follow his/her instructions for usage. Additionally, you’ll want to report any unexpected adverse reactions and/or unwanted side effects as soon as they are noticed. Do not stray from the dosing guidelines that your doctor recommends, as this could have serious, potentially life-threatening consequences. Moreover, be sure to commit to regular checkups during the detoxification process so that your doctor can ensure your safety.
- Calibrate dosing: An experienced medical doctor will be able to determine the dosage range of baclofen that’s safe to administer during opiate detoxification. A majority of individuals receiving baclofen will end up taking between 15 mg and 80 mg per day in divided doses to help with their opiate withdrawal. The exact dosage assigned to you will depend on co-administered substances (and their respective dosages) plus your medical history. The aim should be to take the minimal effective dose of baclofen, or lowest quantity needed to help with opiate detox. By using the smallest dose of baclofen necessary, the likelihood of adverse effects, unwanted side effects, and severe discontinuation symptoms from baclofen – can be minimized.
- Continued usage: If you are working closely with a doctor and regularly reporting your opiate detoxification progress, your doctor should be able to determine how long you’ll need to continue using baclofen. Most people continue using baclofen for weeks or months on an “as-needed” basis until they feel as though they’ve weathered most of the opiate withdrawal storm. The duration over which baclofen is deemed medically helpful in managing opiate detoxification will be subject to individual variation. Some individuals may only need baclofen for a couple of weeks, whereas others may need it for several months.
- Gradual taper: Eventually you will have made it through the most debilitating stages of opiate withdrawal and the usage of baclofen will no longer be necessary. When your doctor thinks you can handle it, he/she will gradually taper you off of baclofen. Tapering is necessary to avoid debilitating withdrawal symptoms associated with abrupt (“cold turkey”) cessation such as: seizures, hallucinations, delusions, and tremor. Do not discontinue baclofen at a faster rate than your doctor recommends as this could be dangerous.
Have you taken baclofen for opiate withdrawal?
If you’ve taken baclofen to help manage symptoms of opiate withdrawal, share your experience in the comments section below. From your perspective, was baclofen an ineffective, slightly effective, or extremely effective medication in the management of your opiate withdrawal symptoms? In the event that someone asked you to rate the therapeutic value of baclofen on a scale of 1 to 10 (with “1” being ineffective and “10” being extremely effective) for the management of opiate withdrawal symptoms, what number would you assign it?
Assuming you considered baclofen to be slightly or extremely useful in your opiate detoxification, which were the symptoms that it most effectively managed? To help others get a better understanding of your situation, provide some details associated with your baclofen usage including: dosage, frequency of administration, cumulative duration of usage, and co-administered substances. Also provide some additional information such as: the history of your opiate usage, intensity of your detoxification symptoms, and/or any comorbid neuropsychiatric disorders that may have complicated the process.
For those that utilized baclofen over a longer-term (e.g. several months), did it continue providing substantial therapeutic benefit or did it benefit diminish over time? In any regard, there are mounting data and anecdotes supporting the efficacy of baclofen for the treatment of opiate detoxification syndrome. That said, more supportive evidence is needed in larger randomized controlled trials before baclofen can be recommended as a first-line intervention during opiate detoxification.