Tapering off of baclofen while in an inpatient or outpatient treatment program is important. Baclofen withdrawal tends to be more severe for those who took high doses of baclofen and/or those who use the injectable form of baclofen. For this reason, it’s highly recommended that anyone experiencing misuse of baclofen undergo medication-assisted treatment, starting with medical detox. The baclofen withdrawal symptoms may include severe side effects and can be life-threatening. In fact, it can cause relapse because of the intense side effects and cravings that most people experience during withdrawal.
FDA Drug Information
Central amygdala extracellular signal- regulated kinase signaling pathway is critical to incubation of opiate craving. Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Castellano C, Cestari V, Cabib S, Puglisi-Allegra S. Strain-dependent effects of post-training GABA receptor agonists and antagonists on memory storage in mice. Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions. Inflammation effects on glutamate as a pathway to neuroprogression in mood disorders. Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders.
A molecular mechanism for choosing alcohol over an alternative reward. Differential distribution of GABA(B1) and GABA(B2) receptor mRNAs in the rat brain. Regional distribution and cellular localization of gamma-aminobutyric acid subtype 1 receptor mRNA in the rat brain. GABA(B) receptor heterodimer-component localisation in human brain.
Targeting the GABAB receptor for the treatment of depression and anxiety disorders. One RCT found that baclofen administration reduced alcohol consumption in anxious patients, but not in patients with low levels of anxiety (55). On the other hand, baclofen failed to modify alcohol consumption in other studies in which participants had high (51) or low (59) baseline anxiety levels. In this study, baclofen administration reduced alcohol consumption in anxious patients, but did not induce significant modifications in other participants. One study suggested a relationship between comorbid anxiety and treatment response to baclofen (55). Two laboratory studies investigated the effects of baclofen in non-treatment seeking AUD participants see Table 4; (26, 48).
The medication development field, at large, and the results of recent meta-analyses show baclofen is not exempt from this pattern (65, 68, 69). In addition, the RCTs used different scales to measure the severity of anxiety and/or depression, such as self-reported rating scales (e.g., STAI, BDI, and ZUNG) and interviewer-rated scales (e.g., HAM-A, HAM-D, and MADRS). This finding agrees with data of large epidemiological studies (14, 60). AUD and a second mental disorder may occur independently, or one of the two disorders may have influenced the development of the other one (1, 63).
Clinical Pharmacology for Baclofen
Without it, individuals risk severe and possibly permanent side effects. However, because they are recovering from addictions, these people are at a higher risk of misusing baclofen, which is why it needs to be closely monitored. This means that, while the FDA has approved baclofen for treating the above conditions, it’s also prescribed to treat conditions not yet approved by the FDA. In recent years, medical professionals have also been prescribing baclofen for “off-label” purposes. Baclofen is not a controlled substance in the United States, however, baclofen misuse can be dangerous.
Alterations in brain structure and functional connectivity in alcohol dependent patients and possible association with impulsivity. Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. Decreased neural activity in reward circuitry during personal reference in abstinent alcoholics—a fMRI study. Chaudhri N, Woods CA, Sahuque LL, Gill TM, Janak PH. Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking.
Another study did not find a significant effect of baclofen on either anxiety or depression, which were evaluated using self-reported rating scales (38). One study observed that the average dose received by female patients was lower than the one received by males (27). A series of retrospective studies evaluated the efficacy of baclofen among large samples of AUD patients see Table 2; (27–29, 36–41). In all these patients, baclofen administration led to alcohol abstinence or to a marked reduction in alcohol consumption. In recent years, animal and human studies conducted to evaluate the efficacy of baclofen in the treatment of AUD have yielded contrasting results (19).
Long-Term Network Alterations
This document does not contain all possible side effects and others may occur. Do not take a double dose to make up for a missed one. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule.
It cannot be excluded that that an initial blockage of the dopaminergic systems participates in the remodeling of brain circuits. The state of indifference is always reached after treatment has lasted for a certain amount of time, which is likely a period of remodeling brain circuits. As a whole, these elements are not compatible with a general hypothesis that would posit an inhibition of dopaminergic systems as a central mechanism for the anti-addictive action of baclofen (Table 1). Disinhibition could be possibly linked to a dose-related effect of baclofen on dopaminergic neurons, where a low dose of baclofen activates VTA neurons and a high dose inhibits them (50, 51). Microinjection of baclofen in the nucleus accumbens also decreases binge-like alcohol drinking (73). The first is the fact that baclofen has clear anti-rewarding effects.
- If you’re looking for a trusted team of providers who can help guide you toward the right treatment plan, Zinnia Health can help.
- The withdrawal period is when your brain and body adjust to not having baclofen in your system.
- However, its sedative effects can lead to an escalation in dosage without medical guidance, tipping the balance from therapeutic use to dependency and abuse.
- If the sight of alcohol has no more effect than looking at nappies or washing powder, the effective dose of baclofen has been reached.” Patients indifferent to alcohol are no longer concerned or stressed by the sight of alcohol.
What should I do if I miss a dose of baclofen?
- Maccioni P, Fantini N, Froestl W, Carai MA, Gessa GL, Colombo G. Specific reduction of alcohol’s motivational properties by the positive allosteric modulator of the GABAB receptor, GS39783—Comparison with the effect of the GABAB receptor direct agonist, baclofen.
- In all studies, participants received daily doses of baclofen ranging from 30 to 145 mg and were monitored from 4 to 52 weeks.
- Pertussis toxin blocks 5-HT1A and GABAB receptor-mediated inhibition of serotonergic neurons.
- Residential treatment is often preferred to the outpatient alternatives because of the around-the-clock care and support provided.
Intra-VTA activation of GABA(B) receptors modulates accumbal dopamine during ethanol seeking behavior. Lorrai I, Maccioni P, Gessa GL, Colombo G. R(+)-baclofen, but not S(−)-baclofen, alters alcohol self-administration in alcohol-preferring rats. The γ-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol in ethanol-dependent rats. Effect of baclofen on alcohol and sucrose self-administration in rats. Assessment of GABA-B, metabotropic glutamate, and opioid receptor involvement in an animal model of binge drinking. Terrier J, Ort A, Yvon C, Saj A, Vuilleumier P, Lüscher C. Bi-directional effect of increasing doses of baclofen on reinforcement learning.
Baclofen in the Treatment of Patients With Alcohol Use Disorder and Other Mental Health Disorders
If the desire to drink alcohol is ignited by the sight of wine and spirits, the baclofen dose should continue to be increased progressively. The long experience of baclofen prescription in AUD shows that this abrupt occurrence of a state of indifference at a given dose is common. Ameisen progressively increased the dose of baclofen up to 270 mg/day, and became completely indifferent to alcohol at that dose. GABA-B-receptor activation alters also the activity of dopamine, serotonin, norepinephrine, GABA and glutamate, which are prominent neurotransmitters implicated in alcohol dependence and are involved in the modulation of brain networks.
Why Do People Take Baclofen?
A few case reports describe the results obtained by the use of baclofen in AUD patients see Table 1; (30–35). The search terms used included alcoholism or AUD or alcohol dependence AND baclofen. Baclofen is a GABAB receptor agonist approved for clinical use as a muscle relaxant. Furthermore, disulfiram should not be used in patients who are not capable of understanding the risks of consuming alcohol while they are taking disulfiram.
It is the addition of 10 mg that abruptly and completely changed his attitude toward alcohol. At the dose of 260 mg/day, he was not indifferent at all. Indifference to alcohol is a special phenomenon. Transcranial Magnetic Stimulation (TMS) targeted to the dorsal anterior cingulate cortex (dACC) has been shown to reliably suppress craving (83, 96); a similar effect has been found with Deep Brain Stimulation (DBS) targeted in the nucleus accumbens (84).
However, baclofen makes patients sometimes feel dull, apathetic, and joyless (approximately 15% of patients), suggesting, rather, a state of atypical depression that does not meet the criteria of a major depressive episode. On the other hand, inhibition of dopaminergic systems has been consistently related to apathy, anhedonia and depression (78). And when a disinhibitory effect occurs at a low dose, it is almost never followed by a state of inhibition when doses are increased, as should be the case if baclofen had a dose-dependent biphasic effect.
Indeed, both these studies (55, 64) evaluated the efficacy of baclofen in modifying the severity of anxiety or depression among AUD patients not affected by severe mental disorders. The results show that the majority of AUD patients treated with baclofen and described by the case reports, as well as the observational and retrospective studies, suffered from anxiety and/or mood disorders. In both studies, baclofen amplified the subjective effects of alcohol, which was suggested as a potential biobehavioral mechanism of how baclofen may affect alcohol drinking (26, 48). The other one did not report significant effects of baclofen on either alcohol consumption, cue-elicited craving, or anxiety levels (26). This review indicates that the most frequent psychiatric comorbidities in patients affected by AUD undergoing baclofen treatment are baclofen addiction potential anxiety and mood disorders. In recent years, animal and human studies have been conducted to evaluate the efficacy of baclofen, a GABAB receptor agonist approved for clinical use as a muscle relaxant, in the treatment of AUD.