Dyslexia Improvement in Medication Trial

Dyslexia or developmental reading disorder is a common learning disorder affecting about 5% of the school age population.

Treatment of dyslexia is difficult and typically is focused on special education classes and reading exercises.

Medication treatment for dyslexia is nearly unheard of as no FDA-approved drug is available for the condition.

However, a recent randomized clinical drug trial found evidence to support the potential use of atomoxetine for dyslexia.

Atomoxetine is a drug approved for attention deficit hyperactivity disorder but it has not received much attention in dyslexia or other learning disorders.

Dr. Sally Shaywitz of Yale University along with colleagues recently published results of their clinical trial of atomoxetine in dyslexia with the following key design and results:
Study population: Children and adolescents between 10-16 years of age with a DSM-IV-TR diagnosis of dyslexia alone (N=58) or dyslexia and ADDH (N=124).
Medication intervention: atomoxetine 1.0 to 1.4 mg/kg/day or placebo
Outcome measures: Woodcock Johnson III, Comprehensive Test of Phonological Processing, Gray Oral Reading Test and Test of Word Reading Efficacy
Results: Atomoxetine improved reading scores in both the dyslexia alone and dyslexia and ADHD groups compared to placebo

The authors note in the discussion that their study suggests the potential for atomoxetine as an adjunct to traditional behavioral and academic interventions in the treatment of dyslexia.

This study will need replication. It might also prompt further study of other stimulant medications such as methylphenidate in dyslexic populations.

Readers with more interest in this trial can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Shaywitz S, Shaywitz B, Wietecha L, Wigal S, McBurnett K, Williams D, Kronenberger WG, & Hooper SR (2016). Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial. Journal of child and adolescent psychopharmacology PMID: 27410907

Bupropion: A Non-stimulant ADHD Drug Treatment

Stimulant drugs including dextroamphetamine (Adderall) and methylphenidate (Ritalin) remain among the most common and effective drug treatments for attention deficit hyperactivity disorder (ADHD).

Alternative to stimulant drugs are needed to expand treatment options for clinicians and patients.

One problem with the stimulants is the potential for misuse and diversion of prescription drugs to illicit drug use.

One non-stimulant FDA approved drug (atomoxetine/Strattera) is available in the U.S.

An additional drug of interest for treatment of ADHD is the antidepressant drug bupropion (Wellbutrin). Bupropion is not a selective serotonin reuptake inhibitor like the most commonly prescribed antidepressants. It appears to target other neurotransmitters like dopamine that may be more relevant in the pathophysiology of ADHD.

Bupropion has not received full clinical trial attention and is not an FDA approved drug in the U.S. Nevertheless, there is some research suggesting it may be useful in ADHD.

A recent study from Iran summarized the results of a randomized, double-blind trial of bupropion in 42 adults with ADHD.

This study found the following results:

• A statistically superior reduction in ADHD symptoms for bupropion vs controls (-43% v -18%)
• The most common side effects with bupropion were agitation, fatigue, somnolence and anxiety
• Side effect frequency in the bupropion group was not statistically different than in the control group although small sample size may have contributed to reduced power to find a difference (type II error)

The authors note that the maximum dose of bupropion in their study was only 150 mg per day. Doses as high as 300 mg per day are common for the treatment of depression. If tolerated, higher doses may be able to further reduce symptoms of ADHD.

A recent meta-analysis examined the efficacy and acceptability of four drugs including bupropion for ADHD in children and adolescents.

This study found bupropion to have lower efficacy compared to the standard stimulant drugs in ADHD.

Nevertheless, bupropion may have some clinical utility for ADHD in adults. Bupropion is approved for smoking cessation and major depression. Adult smokers with ADHD or depressed adults with ADHD may benefit from a drug trial of bupropion.

As noted, bupropion has not been approved by the FDA for ADHD. Any use of this drug for ADHD is off-label. Drug selection and treatment for ADHD requires assessment by a qualified medical professional along with clinical monitoring for safety and efficacy.

Readers with more interest in the two studies discussed in this post can find access to the abstracts by clicking on the PMID links in the citations below.

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Hamedi M, Mohammdi M, Ghaleiha A, Keshavarzi Z, Jafarnia M, Keramatfar R, Alikhani R, Ehyaii A, & Akhondzadeh S (2014). Bupropion in adults with Attention-Deficit/Hyperactivity Disorder: a randomized, double-blind study. Acta medica Iranica, 52 (9), 675-80 PMID: 25325205 

Stuhec M, Munda B, Svab V, & Locatelli I (2015). Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: A meta-analysis with focus on bupropion. Journal of affective disorders, 178, 149-159 PMID: 25813457

Topiramate Augmentation in Major Depression

Molecular Model of the Drug Topiramate

Currently available antidepressants provide significant relief from major depression in many patients.  However, a significant number of patients receive little or limited relief following an initial trial of a standard first-line drug from the selective serotonin re-uptake inhibitor class of agents.


A common clinical strategy after initial drug non-response and non-remission is to consider pharmacological augmentation.  Augmentation options for clinicians include lithium carbonate, triiodthyronine (thyroid hormone), a second antidepressant, an atypical antipsychotic or adding psychotherapy if it is not already being provided.


Despite the number and range of augmentation options, additional options need to be explored given the persistence of depressive symptoms in many individuals.  A small study from Iran suggests one alternative to consider may be the drug topiramate.


Topiramate is a drug approved by the FDA for the treatment of epilepsy and migraine headaches  in the United States.  It is not approved for the treatment of any primary psychiatric disorder.  The exact mechanism of action for topiramate is unknown although it is known to have effects on the sodium channel, gamma-amino butyric acid (GABA) receptors, glutamate receptors and act as a carbonic anhydrase inhibitor.


Mowla and Kardeh have published a small study of 42 subjects randomized to topiramate or placebo.  The key elements of the study include:

• Subjects: Adults with DSM-IV major depressive disorder who had failed to respond to eight weeks of treatment with an SSRI drug (fluoxetine, citalopram or sertraline)
• Drug: Topiramate 25 mg per day increased by 25 mg per week throughout the trial (mean dosage 175 mg/day) or placebo
• Clinical trial design: Double-blind, randomized controlled trial with primary outcome measure the Hamilton Depression Rating scale (HAM-D) administered by a psychologist not involved in treatment

Fifty three subjects started the study with 11 dropouts (six in the topiramate group and five in the placebo group).  HAM-D scores statistically decreased more in the topiramate group (21.6 at baseline to 14.7 at 8 weeks) than in the placebo group (21.9 at baseline to 20.8 at 8 weeks).


Since a score of seven or more is considered remission in MDD, the mean score of 14.7 in the topiramate groups suggests significant residual symptomatology.  The authors do not provide the number of subjects meeting remission criteria in the topiramate and placebo groups by 8 weeks.


Nevertheless, topiramate has some potential significant advantages in the treatment-resistant major depression population.  First, it is a generic drug and would have some cost advantages in comparison to some of the other options.  Second, topiramate it typically weight neutral or produces a slight weight reduction.  Most antidepressants increase weight over time so this might be an important advantage.  Third, topiramate might hold an advantage in treatment of MDD populations with migraine or epilepsy--disorders with an indication for the drug.


This study is too small to change clinical practice patterns or guidelines.  Additional larger replication studies need to be considered.  

Molecular model of the drug topiramate from Wikipedia Creative Commons file released to the public domain.  Author of the model is: Fvansconsellos

Mowla A, & Kardeh E (2011). Topiramate augmentation in patients with resistant major depressive disorder: a double-blind placebo-controlled clinical trial. Progress in neuro-psychopharmacology & biological psychiatry, 35 (4), 970-3 PMID: 21291943