A Phase IV (post-marketing), sponsored by GlaxoSmithKline suggested that the cognitive side effects could be more in common with topiramate than with lamotrigina. In studies with healthy volunteers in May 2007, comparing the two mediations,
Therapeutic doses of topiramate in the case of bipolar disorder, produced greater cognitive deficits than lamotrigine, including loss of short-term memory and difficulties in retrieving words. This effect has led to the occasional use of dopamax by some unhappy customers.
Affectivity has been published flat in> 75% of patients (n = 60). The most common side effects include changes in taste (carbonated beverages, especially diet sodas and beer) and feelings of pins and needles in the head and limbs.
Some less common side effects include cognitive deficits (especially evocation of words), dullness and lethargy, kidney stones, mismatch of the functions fine motor, visual abnormality and transient visual loss permanent (see below warnings from the FDA), weight loss, abdominal pain, profuse sweating, menstrual disturbances, changes in taste, pharyngitis, sinusitis, diplopia, rash, leukopenia, fatigue, dizziness, insomnia, anxiety, depression, paresthesia, diarrhoea, nausea, dyspepsia, constipation and dysmenorrhea oral moisture.
Rarely inhibition of carbonic anhydrase may be strong enough to cause clinically significant metabolic acidosis. The most common side effects leading to discontinuation of therapy with topiramate were:
Psychomotor Slowing (4.1%)
Memory problems (3.3%)
Side effects found in> 10% of subjects in at least one study listed in order of prevalence are:
(* The on the rate of [%] are the same or higher than the rate of side effects)
Headache (23.8%) * [25.9%]
paresthesia (numbness and tingling) (23.1%)
upper respiratory tract infections (17.5%)
somnolence (15.4%) * [16.1%]
anorexia (appetite loss) (13.3%) * [5.6%]
insomnia (11.9%) * [11.2%]
memory problems (11.2%)
vertigo (10.5%) * [10.5]
The administration of food and medicines USA (FDA) has caused notice, alerting physicians who prescribe topiramate to patients at risk of vision loss (blindness). Acute myopia and secondary angle closure glaucoma can cause transient blindness (reversible) or permanently in a small subset of patients who take topiramate regularly.
Symptoms, which typically start within the first month of use include blurred vision and eye pain. If treated early in its course, discontinuation of treatment, along with other measures deemed prudent by the physician or ophthalmologist, may halt the progression of eye damage and may reverse the visual mismatch.
It is advisable for patients taking topiramate and to feel pain around the eyes, or notice vision loss, visual acuity or blurred vision. If this manifests they must consult their doctors as soon as reasonably possible. According to the FDA: “In more than 825,000 patients as of August 17th 2001, there were a reported 23 cases: 22 adults and a child. It is generally recognized that post-marketing data is subject to a notification substantially below normal.”
Other side effects are serious is the development of osteoporosis in adults and children (the affected bones break more easily) and rickets (abnormal growth and deformed bones). Topiramate may also slow the growth of children. All of these conditions should be detected early in conducting regular clinical examinations of patients.
Other post-marketing research found the risk of decline in sweating and hyperthermia. Pediatric patients (children) are especially susceptible to this side effect. It is recommended that children treated with topiramate to be monitored carefully in search of decreased sweating and increased body temperature, especially in hot climates.
All patients, particularly those who have other predisposing factors, will be instructed to maintain adequate fluid intake to minimize the risk of kidney stone formation.
Since topiramate inhibits carbonic anhydrase concomitant use of other inhibitors, such as acetazolamide, this can lead to an increased risk of kidney stones. Enzyme inducers (e.g. carbamazepine): The elimination of topiramate may be increased, possibly requiring escalating doses.
Phenytoin: Topiramate may increase plasma levels of phenytoin.
The same topiramate is a weak inhibitor of CYP 2C19 and induces CYP 3A4. Pajo topiramate decreases plasma levels of estrogen (e.g. OCs) and digoxin.
Alcohol can cause increased sedation or drowsiness, and increased risk of attack. As was stated on the label published on page 14 of the FDA’s website on 6/29/2005 “conditions or therapies that predispose acidosis may have an additive effect of baking diminishing effects of topiramate”. This labelling is absent from any discussion of interactions with narcotics (drugs that are known to promote respiratory acidosis). This discussion is contained on page 14 and is in the field of metabolic acidosis.
To avoid early side effects (e.g. Cognitive dysfunction) the initial dose is usually low and is increased step by step. The usual starting dose is 25-50mg daily in 2 doses only. Recommended are increases of 25 to 50mg every 1 to 2 weeks. Common dosages for maintenance therapy are 100 to 200mg daily. The highest possible dose is 1000mg daily in divided doses.
Symptoms of overdose may include, but are not limited to, the following:
Dizziness, drowsiness, tiredness
Blurred vision, double vision
Loss of coordination
Inability to respond to external stimuli
Loss of consciousness
confusion and coma
Loss of appetite and vomiting
Palpitations or irregular heartbeat
There is no specific antidote. Treatment is entirely symptomatic.