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Clonidine For ADHD: An Effective Treatment & Adjunct

Clonidine is a drug that is commonly prescribed to treat high blood pressure.  Clonidine is also commonly used as a treatment for anxiety and as an intervention to minimize drug withdrawal symptoms.  On occasion, it is prescribed off-label for the treatment of PTSD, borderline personality disorder, stress, and insomnia.

It functions primarily as an Alpha-2 adrenergic agonist, meaning it stimulates Alpha-2 receptors to reduce blood pressure.  Regionally, it primarily targets Alpha-2 receptors in the vasomotor area of the brainstem.  Upon binding to these receptors, it inhibits the release of norepinephrine and decreases extracellular calcium levels – ultimately decreasing activation of the sympathetic nervous system.

A lesser known use for Clonidine is to treat ADHD.  As of 2010, the drug was approved by the FDA as an atypical ADHD medication.  It is thought to treat attentional-deficits specifically by ramping up norepinephrine in the prefrontal cortex.  The reduction of physiological stimulation from the sympathetic nervous system, coupled with an increase in prefrontal norepinephrine is thought to increase both calmness and concentration.

Clonidine for ADHD: The Research

Below is some research highlighting the efficacy of Clonidine for the treatment of ADHD.  Studies analyzing Clonidine for the treatment of attentional deficits dates back to the 1990s.  Most research suggests that Clonidine is inferior in efficacy to psychostimulants and therefore should be regarded as a second-line or adjunct option.

1993: In 1993, a French journal discussed the usage of Clonidine in child psychiatry.  The authors noted that Clonidine may be an effective option for the treatment of ADHD.  They noted that when administered at microdoses of just 0.004 mg to 0.005 mg (4 to 5 mcg), it can reduce ADHD symptoms by 25% to 50% depending on the individual.

The authors noted that the drug produced minimal unwanted side effects.  They also distinguished the mechanisms of Clonidine from methylphenidate.  In particular, they suggested that methylphenidate is likely superior to Clonidine for children with major attention deficits and/or moderate hyperactivity.  However, they suggest Clonidine is likely superior to methylphenidate for children with hyperarousal, hyperactivity, and/or aggression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8275901

1996: A study published in 1996 analyzed the efficacy of Clonidine in treating ADHD-related sleep disturbances.  It is well-documented that individuals with attention-deficit/hyperactivity disorder often suffer from poor sleep quality, insomnia, and possibly an insufficient duration of sleep.  Researchers used a computer database to review the usage of Clonidine among those with ADHD-related sleep abnormalities.

A total of 62 cases were analyzed with a total of 42 children and 20 adolescents.  In all cases, individuals were rated on a retrospective basis at “baseline” and after treatment with Clonidine.  Ratings assessed the type of disturbance experienced as well as severity of those disturbances.

Results suggested that approximately 85% of individuals taking Clonidine experienced “significant” or “very significant” improvement based on global assessments of sleep improvement.  Doses of Clonidine taken at night ranged from 0.05 mg to 0.8 mg – with an average dosage of approximately 0.15 mg.

The patients had been reported taking Clonidine for approximately 35 months.  There were no differences in efficacy based on age, gender, comorbidity, or other medications.  Some adverse effects were reported in approximately 1/3 participants.  Based on the results, researchers suggest that Clonidine may be an effective treatment for sleep disturbances induced by (or related to) ADHD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8935206

1999: In the late 1990s, considerable research began to surface that documented Clonidine’s efficacy for the treatment of ADHD.  A meta-analysis published in 1999 reviewed the literature of clinical usage of Clonidine to reduce symptoms of attentional-deficits and hyperactivity.  The literature review spanned over the course of 19 years (1980 to 1999) based on a total of 39 studies.

Despite the fact that there were 39 studies analyzed, only 11 were thorough enough to be included in this literature review.  Results from the meta-analysis suggested that Clonidine was moderately effective in treating ADHD symptoms among children and adolescents.  Researchers noted that Clonidine could be considered a feasible second-line treatment for ADHD, but psychostimulants remain superior in terms of efficacy and side effects.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10596256

2008:  A study published in 2008 evaluated both the safety and efficacy of Clonidine as a treatment for attention-deficit/hyperactivity disorder (ADHD).  More specifically, this study analyzed Clonidine when used alone or in combination with the highly-popular psychostimulant methylphenidate (Ritalin).  The study took place over a period of 16 weeks and was regarded as being randomized, double-blind, and placebo-controlled.

A total of 122 children ages 7 to 12 participated in the study and no subtypes of ADHD were excluded from participation.  The participants were divided and placed into one of four groups: standalone Clonidine, standalone methylphenidate, Clonidine plus methylphenidate, or a placebo.  All doses were titrated and adjusted over the course of the first eight weeks and the study was continued for an additional eight weeks.

Participants were evaluated at baseline and following 16 weeks of treatment.  Evaluations were conducted using the Conners Teachers Abbreviated Symptoms Questionnaire (CTASQ). Secondary evaluations were conducted using the Conners Abbreviated Symptoms Questionnaire for Parents and the Children’s Global Assessment Scale.

Results indicated that Clonidine did NOT improve ADHD symptoms according to the CTASQ.  Those treated with the methylphenidate experienced significant improvement compared to others.  Those treated with Clonidine experienced improvements on the CASQ for Parents and the Children’s Global Assessment Scale.  That said, those taking the Clonidine also reported significantly greater levels of sedation.

Based on the evidence from the study, Clonidine produced moderate symptomatic improvement, but also significant sedation.  Those treated with methylphenidate did not report sedation and experienced significantly greater improvement.  Researchers suggest that methylphenidate is superior in both efficacy and tolerability among children with ADHD when compared to Clonidine.

Despite the superiority of methylphenidate, researchers noted that when Clonidine was used alone or with methylphenidate, it is still safe and well-tolerated in childhood ADHD.  They also noted that most side effects associated with Clonidine subside within 6 to 8 weeks of usage.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18182963
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18182964

2009: Quality of life should be prioritized among individuals diagnosed with ADHD.  Treating symptoms with pharmaceutical medications can result in functional improvement for a person with ADHD, but may not improve their quality of life.  Certain medications may actually worsen quality of life as a result of unfavorable side effects.

A study published in 2009 analyzed the effects of Clonidine, methylphenidate, and a combination of the drugs – on “family” quality of life among those with ADHD.  Family quality of life was measured in a 16-week, placebo-controlled, double-blind study.  Participants included 122 children from age 7 to 12 that had been diagnosed with ADHD.

Measures of quality of life were measured with the “Daily Hassles Scale” and the “Impact on Family Scale.”  A baseline measure was taken as well as another after 16 weeks.  Results indicated that all treatment groups (Clonidine, methylphenidate, and combination) experienced an improved quality of life compared to a placebo group.  Notable reductions in ADHD symptoms were also reported.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830226/

2009: In 2009, researchers compared the efficacy of two second-line ADHD treatments: Clonidine and the anticonvulsant drug Carbamazepine.  Both drugs are low cost, and may be more suitable for usage in developing countries compared to psychostimulants.  Although neither drug is regarded as superior in efficacy to psychostimulants, they are considered widely available and favorable in terms of cost.

Participants for this study included 50 children (ages 4 to 12) with ADHD from South India.  The study spanned over a period of 2 years.  Results indicated that Clonidine was an effective treatment for reducing both hyperactivity and impulsivity symptoms compared to Carbamazepine.  Researchers concluded that Clonidine is a safe, cheap, and effective option for the treatment of ADHD in children – particularly those with a significant degree of hyperactivity and impulsivity.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19203986

2011: Research published in 2011 highlighted the efficacy of Clonidine XR (extended-release) for the treatment of ADHD in children and adolescents (6 to 17 years old).  Authors reflected upon multiple randomized, double-blind, placebo-controlled “Phase III” trials.  These trials spanned over 8-weeks and compared the efficacy of Clonidine XR to that of a placebo.

ADHD symptom severity was measured with the ADHD-RS-IV (ADHD Rating Scale); measures were taken at “baseline” (e.g. pre-treatment) and at various endpoints.  At dosages of 0.2 mg and 0.4 mg per day, Clonidine XR was found significantly more effective than a placebo for reducing ADHD symptoms.  The second study analyzed the effect of Clonidine XR as an adjunct to a standard psychostimulant medication.

In this study, Clonidine XR was added as an adjunct to a psychostimulant.  The Clonidine was administered at flexible dosing, ranging between 0.1 mg and 0.4 mg.  Participants experienced significant reduction in ADHD symptoms based on the ADHD-RS-IV after 5-weeks of treatment.  Researchers noted significant symptomatic reductions after just 2 weeks of adding Clonidine XR as an adjunct.

Clonidine XR was considered to be well-tolerated and effective when used as a monotherapeutic option or as an adjunct.  It can be concluded that Clonidine is a safe, non-stimulant option for the treatment of ADHD among children and adolescents between the ages of 6 and 17.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21888447
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21555501

2011: A review of evidence published in 2011 analyzed the efficacy of Clonidine for the treatment of ADHD among children and adolescents.  The review evaluated both the safety and efficacy of Clonidine spanning from 1996 to 2011.  The evaluation was conducted based on 10 clinical trials from the Medline database.

Of those 10 trials, 8 were considered double-blind and placebo controlled.  Both the immediate-release (IR) Clonidine and extended-release (XR) Clonidine were evaluated as monotherapeutic or adjunct treatments.  One of the studies found that Clonidine was ineffective for improving task-performance, but the sample size was small.

All studies reported that both the IR and XR format of Clonidine were well-tolerated.  Researchers were unable to conclude whether the efficacy differs between the IR and XR formats due to no head-to-head comparisons.  Results from this analysis suggest that Clonidine IR and XR are likely effective and safe as monotherapeutic and adjunctive treatments among those with ADHD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24600280

2012: Researchers published a review in 2012 discussing the fact that nearly 1/3 children and adolescents with ADHD have poor responses to standard first-line psychostimulant medications.  These researchers suggested that among individuals with poor responses to psychostimulants, adding Clonidine may result in improved symptomatic reduction.

They theorize that the addition of an Alpha-2 adrenorceptor agonist will work synergistically with psychostimulants via the prefrontal cortex.  Researchers note that early studies with Clonidine utilized the “IR” (immediate-release) version may have been more prone to side effects due to the “IR” achieving higher concentrations at a rapid rate.  By comparison, the “XR” (extended-release) version offers a slower, steady release and may minimize side effects and/or tolerability issues.

These researchers are suggesting that the newer “XR” formulation of Clonidine may prove to be better tolerated than the “IR” formulation, while providing longer-lasting relief from ADHD symptoms.  Researchers note that Clonidine remains effective as both a monotherapeutic and adjunct treatment for ADHD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22462040

Is there any evidence suggesting Clonidine is ineffective?

There appears to be no significant evidence suggesting that Clonidine is ineffective for the treatment of ADHD.  Nearly every published study highlights some degree of improvement in regards to ADHD symptoms.  While the improvements may not have been as significant as those produced by psychostimulant drugs like methylphenidate, they are still regarded as clinically significant compared to a placebo.  The FDA approved Clonidine for the treatment of ADHD, solidifying its status as an effective option.

Advantages of Using Clonidine for ADHD

Below is a list of various advantages associated with using Clonidine for the treatment of ADHD.  A primary advantage associated with Clonidine compared to other drugs is that it doesn’t stimulate the sympathetic nervous system, allowing an individual to remain calm rather than anxious as a result of the stimulation.

  • Adjunct drug: A notable advantage associated with Clonidine is that it can be used as an adjunct treatment for ADHD. This means a psychiatrist can prescribe it along with a psychostimulant like Adderall, Vyvanse, or methylphenidate.  When used as an adjunct, it may produce a greater effect than using a standalone psychostimulant.
  • Appetite neutral: Many psychostimulant drugs reduce appetite, which can be favorable if you’re overweight – but not so favorable if you’re already skinny or at a healthy weight. For most people, Clonidine won’t have a significant effect on appetite.  In other words, you’ll likely maintain your homeostatic appetite.
  • Anxiety reduction: If you have ADHD and comorbid anxiety, this drug may be a preferred option. Most people know that benzodiazepines are linked to dementia and are habit forming –  valid reasons to avoid this class of drugs.  If you have ADHD, benzodiazepines may further impair your cognitive function.  Many people take Clonidine for anxiety due to the fact that its regarded as safe and is effective – plus it improves concentration.
  • Blood pressure reduction: If you have ADHD and high blood pressure, this medication may help you kill two birds with one stone. Your doctor may be able to configure a dosage that reduces your hypertension, while simultaneously improves your cognitive function.
  • Calm focus: The focus that you experience while taking Clonidine may be preferred due to the fact that your nervous system is actually calmed. Clonidine shuts off excess sympathetic activity, while releasing norepinephrine in the prefrontal cortex.  This may allow you to feel physically calm, but mentally focused.
  • Children / adolescents: Clonidine has been studied extensively among children and adolescents and is considered both safe and effective. Those concerned about usage of psychostimulants during childhood or adolescent years may prefer Clonidine.  Clonidine isn’t as potent as a psychostimulant drug and may have a favorable mechanism of action.
  • Less potent: The potency of Clonidine is thought to be significantly less than psychostimulants. Although it is difficult to compare a nonstimulant medication with a psychostimulant, it is clear that the cortical effects are more extreme with the psychostimulant.  If you only have a mild case of ADHD, Clonidine may be preferred over psychostimulants.
  • Prefrontal cortex activation: Using Clonidine is still known to activate the prefrontal cortex. It ramps up production of norepinephrine in this region.  Norepinephrine is regarded as a stimulatory neurotransmitter that is known to increase focus.
  • Side effects: The side effects experienced by those taking Clonidine are regarded as being relatively mild in intensity. Additionally, among those who experience side effects, most tend to subside after 6 to 8 weeks of treatment.  Therefore there’s a relatively low risk of unfavorable side effects – especially when taken over a long-term.
  • Sleep improvement: In some of the aforementioned studies, Clonidine was noted as improving ADHD-related sleep disturbances. It is well-known that Clonidine can help insomnia and improve sleep quality.  Hence, many doctors prescribe it off-label to help with drug withdrawal and conditions like insomnia.
  • Weight neutral: While a select number of people may experience weight loss or gain while taking Clonidine, fluctuations in body weight are unlikely. Therefore most professionals regard Clonidine as a weight neutral drug. This may be preferred over a psychostimulant drug due to the fact that they promote weight loss by speeding up metabolism, increasing satiety, and boosting energy levels.
  • Withdrawal: The discontinuation effects of Clonidine are thought to be significantly less debilitating than those of a psychostimulant. If you were to compare reports of Clonidine withdrawal symptoms to Adderall withdrawal symptoms, you’d likely find that those associated with Clonidine are less debilitating.  Some professionals may even go as far as to suggest that there are no significant discontinuation effects associated with Clonidine.

Disadvantages of Using Clonidine for ADHD

Like any drug, Clonidine should not be considered a utopian option.  Some people may find that its ineffective for their ADHD and/or may even worsen their symptoms.

  • Brain fog: Due to the fact that Clonidine reduces activity of the sympathetic nervous system, some people may find that it impairs their focus or causes “brain fog.” The Alpha-2 adrenergic agonistic effect may result in sedation that ultimately impairs a person’s ability to concentrate.  In many cases, the decrease in focus is a result of a temporary adjustment, but others may find that their particular neurophysiology responds poorly to Clonidine.
  • Less effective: The efficacy of Clonidine is regarded as being less than that of a psychostimulant medication. While for those with milder cases of ADHD, this reduced potency may be appealing – most people want to take the most effective drug.  If your goal is to try the universally most effective drug, a psychostimulant will likely be preferred over Clonidine.
  • Low blood pressure: If you already have naturally low blood pressure and/or take high amounts of Clonidine, you may not like the increased reduction resulting from the drug. Excessive low blood pressure may result in dizziness, lightheadedness, nausea, blurred vision, fatigue, and… concentration impairment.
  • Sedation: The most commonly reported side effect associated with Clonidine is that of sedation. While this sedation may “wear off” over the course of treatment (e.g. after 6 to 8 weeks), others find that the sedation never fully subsides.  If the drug is making you overly sedated, this may interfere with various aspects of your life including: physical performance and energy levels.

How does Clonidine compare to psychostimulants?

Upon comparison to other psychostimulants, Clonidine is less effective for the treatment of ADHD.  Clonidine produces a moderate reduction in symptoms, while psychostimulants are known to produce an extreme reduction in symptoms.  It’s like saying that Clonidine is effective, whereas a psychostimulant is “super-effective” – it’s just not quite on the same level of efficacy as the dopaminergic drugs.

Clonidine has a totally different mechanism of action compared to psychostimulants that primarily function as dopamine reuptake inhibitors (DRIs).  Clonidine bolsters norepinephrine stimulation in the prefrontal cortex, ultimately improving attentional capacity.  Although Clonidine may not be as effective as first-line psychostimulant treatments – it is still clinically effective and thus has FDA approval for treating ADHD.

Some speculate that Clonidine may be more effective than psychostimulants for treating certain subtypes of ADHD.  Cases of ADHD with prominent features of hyperarousal, hyperactivity, and/or aggression may derive more benefit from Clonidine than psychostimulants.  It is noted as being less effective than psychostimulants for severe attention deficits and moderate hyperactivity.

Is Clonidine plus a psychostimulant more effective?

Researchers have long noted that Clonidine can be used as an adjunct to a psychostimulant.  Clonidine plus a psychostimulant medication for the treatment of ADHD is considered well-tolerated among children and adolescents.  Despite the tolerability of Clonidine along with psychostimulants, there is no conclusive evidence to suggest increased efficacy of the combination when compared to a standalone psychostimulant.

Many experts theorize that by adding Clonidine to a psychostimulant, the combination elicits a synergistic effect – most notably in the prefrontal cortex.  In other words the prefrontal stimulation of the Clonidine adds to the attentional improvements derived from the psychostimulant usage.  Therefore, some individuals may notice significantly greater improvements with Clonidine and a psychostimulant compared to a standalone psychostimulant.

It is unknown as to whether universal responses to the combination produces superior symptomatic improvements when compared to standalone treatment with a psychostimulant.  That said, it is known that the combination is effective, and some individuals may respond favorably to a blending of the mechanisms.

One controlled trial suggests that among those with ADHD and comorbid “tics” – the combination of Clonidine and methylphenidate is superior than either drug as a standalone treatment.  This suggests that in particular cases of ADHD with various comorbidities like “tics,” a combination of treatments may produce preferable outcomes.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22462040
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12679740/

Optimal Usage of Clonidine for ADHD: Who is most likely to benefit?

Not all individuals with ADHD may benefit from Clonidine.  Since Clonidine is regarded as a second-line treatment, it may provide greater efficacy among those with comorbidities that stand to benefit from the drug’s unique mechanism of action.

Anxiety disorders: Those with anxiety disorders and comorbid attentional deficits (or vice-versa) may benefit significantly from Clonidine.  The drug is known to help reduce activity in the sympathetic nervous system and may provide varying degrees of sedation for some individuals.

Certain ADHD subtypes: Those with specific types of ADHD may stand to benefit more from Clonidine than other traditional stimulatory treatments.  It has been suggested that those with “overfocused” ADHD may need to reduce activity in the sympathetic nervous system.  Reduction in this activity may have a cascade effect, thereby reducing high beta waves (e.g. type 2 beta) that may be responsible for this specific subtype.

High blood pressure: There is significant research highlighting the safety and efficacy of Clonidine for the treatment of hypertension (high blood pressure) over the long-term.  If you have high-blood pressure and comorbid attentional problems, Clonidine may be an optimal treatment.

Tic disorders: Clonidine has been found to produce significant reduction in “tics” among those with tic disorders.  Specifically, when Clonidine is combined with a psychostimulant like methylphenidate, tic reduction is more significant than with either drug as a monotherapy.

Tourette’s syndrome: There is evidence that Clonidine may help improve symptoms among those with Tourette’s syndrome.  Therefore if an individual has Tourette’s and comorbid attentional deficits, this medication may be an effective intervention.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518387/
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11865128

Personal experience taking Clonidine…

I’ve personally taken Clonidine, but not consistently enough to evaluate its efficacy for ADHD.  I took the drug to help with situational anxiety.  My psychiatrist had explained that the drug would reduce my anxiety, improve my sleep, and also help with any attention and/or focus difficulties.

Both him and I agreed that taking Clonidine was smarter than taking a benzo due to the preliminary evidence that benzos increase susceptibility to dementia.  I did not take Clonidine every day and therefore have a difficult time evaluating it for attention.  In my experience, I noticed that it made me feel calmer, but I didn’t feel significantly more focus.

The thing I did like about Clonidine is that it did not hamper my cognitive function like Xanax, and as a result of its mechanism of action – may have subtly improved it.  From my subjective perspective, I didn’t notice any significant cognitive improvement or increased attentional capacity – but I wasn’t tracking them either.  My guess is that if I would’ve consistently used the drug, my attention would’ve likely improved.

I like to think of Clonidine as a safer version of benzodiazepines – no dementia link and doesn’t interfere with concentration.  The icing on the cake is that the drug has potential to improve cognitive function and attention as a result of increasing activity in the prefrontal cortex.  Since I wasn’t consistent with my Clonidine usage, it’s impossible for me to report on is efficacy – but I will say that its effect was satisfactory.

Have you tried Clonidine for ADHD?

If you have experience trying Clonidine for ADHD, mention whether you found it effective in the comments section.  To help others get an idea of your situation, discuss the dosage, whether you were on any other medications (e.g. psychostimulants), and any side effects you experienced.  If you are taking Clonidine for another condition (e.g. hypertension), did you find that it improved your focus and/or decreased hyperactivity?

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