Efficacy and tolerability of topiramate in children younger than 2 years old

To evaluate the efficacy and tolerability of topiramate in children with epilepsy younger than 2 years of age, we retrospectively reviewed the records of patients treated at our institution between 2001 and 2003. Thirteen children ages 5 to 23 months, five boys and eight girls, were identified. Seizure types were partial (five), generalized tonic-clonic (three), myoclonic (one), and infantile spasms (four). The mean age at seizure onset was 9.7 months. Topiramate was started at a mean age of 11.4 months (4-23 months). The number of antiepileptic drugs prior to topiramate therapy ranged from zero to four. One patient had been on the ketogenic diet. Topiramate was used as monotherapy in seven children and as polytherapy in six children. Mean follow-up was 14 months. The mean dose of topiramate was 8.8 mg/kg/day (2.5-18 mg/kg/day). The degree of seizure reduction was as follows: > 75% in five (38.5%) children, 50% to 75% in three (23%) children, and 0 to 25% in five (38.5%) children. Three of four (75%) patients with infantile spasms had a > 75% reduction in seizures. Adverse effects occurred in two children, including lethargy, hyperthermia, and anorexia. In children younger than 2 years of age, for whom the antiepileptic drug armamentarium is limited, topiramate appears to be an efficacious and safe therapeutic alternative for a variety of seizure types.     

The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial.

OBJECTIVES: This study has been conducted to assess the efficacy and safety of topiramate in refractory epilepsies in infants and young children. METHODS: A prospective clinical trial was performed in three tertiary care hospitals, on 47 children aged 6-60 months with refractory epilepsy. Topiramate was added to at least two baseline anti-epileptic drugs. The efficacy was rated according to seizure type, frequency and duration. RESULTS: Children with refractory epilepsy were classified according to their clinical, neuro-imaging, and neurophysiological profile into infantile spasms (IS) (9 cases, 19%), Lennox-Gastaut syndrome (LGS) (25 cases, 53%) and other epilepsies (13 cases, 28%). Children were also classified into cryptogenic and symptomatic epilepsy. Topiramate was introduced as add-on therapy in a daily dose of 1 mg/kg/day for 2 weeks, followed by increments of 1-3 mg/kg/day at 2-week intervals, up to a maximum of 10 mg/kg/day. After a minimum treatment period of 6 months, 28 (60%) of the children had a satisfactory response (completely seizure free, or more than a 50% seizure reduction). The remaining 19 children (40%) had an unsatisfactory response (50% or less reduction in seizure frequency, no change or increased seizure frequency). Topiramate appeared to be equally effective in infantile spasms, Lennox-Gastaut syndrome and children with other types of epilepsy, with no significant difference between those with a satisfactory and an unsatisfactory response (p=0.089). There was also no significant difference in response between patients with cryptogenic and symptomatic epilepsy (p=0.360). Mild to moderate adverse effects, mainly somnolence, anorexia and nervousness, were present in 25 (53%) of children. One of the children developed hypothyroidism. CONCLUSION: Although the long term safety and possible adverse effects of topiramate have not been fully established in infants and young children, this study has shown that it is a useful option for children with frequent seizures unresponsive to standard anti-epileptic drugs.     

Prospective study of first-choice topiramate therapy in newly diagnosed infantile spasms

OBJECTIVE: This was a prospective open study to establish the efficacy, tolerability, and problems associated with the use of topiramate as first-choice drug in children with infantile spasms. METHODS: Open-label follow-up study, ranging from 24 to 36 months, of the cases of 54 patients with infantile spasms treated initially with topiramate as first-choice drug. RESULTS: Thirty-one patients (57.4%) were seizure free for more than 24 months; 9 patients were treated with topiramate alone and 22 patients with topiramate plus nitrazepam and/or valproate. In 44 cases (81.4%), the reduction of seizure frequency from baseline was greater than 30%, whereas in 10 cases (18.6%), there was poor or no response. The average dosage applied was 5.2 mg/kg per day (maximum dosage, 26 mg/kg per day; minimum dosage, 1.56 mg/kg per day). Adverse events occurred in 14 patients (26%). They included poor appetite leading to anorexia, absence of sweating, and sleeplessness. CONCLUSIONS: Topiramate proves to be an effective and safe first-choice drug not only as adjunctive but also as monotherapy of infantile spasms in children younger than 2 years.     

Use of topiramate in childhood generalized seizure disorders

Topiramate is a sulfamate derivative of the naturally occurring monosaccharide D-fructose. It was initially approved in the United States as adjunctive therapy for partial seizures in 1997. However, there is increasing evidence that it is effective in the treatment of generalized seizures and epilepsy syndromes. Initially, open-label studies using topiramate as add-on therapy in children with refractory generalized seizure types were performed. These showed improvement in patients with the following generalized seizure types: typical and atypical absence, atonic, myoclonic, generalized tonic-clonic, and juvenile myoclonic epilepsy. Double-blind, placebo-controlled multicentered studies in patients with refractory primary generalized tonic-clonic seizures and epilepsy syndromes were performed. The median reduction in seizure frequency for primary generalized tonic-clonic seizures was 56.7% for topiramate and 9% for placebo. Additionally, 13.6% of topiramate-treated patients were primary generalized tonic-clonic seizure free for the study period. In the topiramate-treated juvenile myoclonic epilepsy patients, primary generalized tonic-clonic seizures were reduced > 50% in 73% of patients. Open-label extension showed that primary generalized tonic-clonic seizures were reduced >50% in 63% of topiramate-treated patients for > or = 6 months, and 16% were primary generalized tonic-clonic seizure free > or = 6 months. Accumulating evidence suggests that topiramate has a broad spectrum of antiepileptic effect. Moreover, life-threatening organ toxicity has not been attributed to topiramate. Topiramate is an effective treatment for refractory generalized seizure types and epilepsy syndromes encountered in children.     

Topiramate for the treatment of infantile spasms

Topiramate is a new antiepileptic drug with a broad spectrum of efficacy. Reports on the use of topiramate for treatment of infantile spasms are limited. We prospectively followed 15 children with recently diagnosed infantile spasms treated with topiramate for efficacy and tolerability. Twelve patients had symptomatic infantile spasms, and two patients had cryptogenic infantile spasms. Topiramate was started at a dose of 3 mg/kg/day and titrated up to a dose of 27 mg/kg/day in 2 to 3 weeks. The primary efficacy measure was comparison of the seizure rate during the 2-week baseline with the median seizure rate during the first 2 months of treatment with topiramate. We also compared baseline electroencephalograms (EEGs) with post-treatment EEGs. The median seizure rate reduction during the first 2 months of treatment was 41% (P = .002). Three patients became spasm free (20%), five had > 50% reduction, and three had at least 25% reduction. Four patients did not respond. Three of 15 patients had clearing of hypsarrhythmia. Topiramate was generally well tolerated, with irritability being the most common side effect. Topiramate was efficacious and well tolerated; one patient discontinued the medication because of adverse effects. (J Child Neurol 2006;21:17-19).     

Newer antiepileptic drugs: advantages and disadvantages

The choice of an antiepileptic drug depends firstly on its efficacy in specific seizure types and epilepsies. However, it is imperative to consider whether possible adverse events will outweigh any benefits. The advantages and disadvantages of vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine and felbamate are considered in some detail, and oxcarbazepine, stiripentol, remacemide, zonisamide and levetiracetam more briefly. Vigabatrin is effective for partial seizures and infantile spasms, but visual field defects are limiting its use. Lamotrigine has a wide spectrum, needs to be prescribed with care. Gabapentin is unlikely to cause adverse effects, but has relatively poor efficacy. Topiramate is widely effective, but can be poorly tolerated. Tiagabine is relatively untried in childhood epilepsies. The use of felbamate is restricted to severe refractory epilepsies. Stiripentol can be effective in severe myoclonic epilepsy in infancy. Zonisamide has a special place in the progressive myoclonus epilepsies. Levetiracetam, remacemide and oxcarbazepine have been used mainly for partial seizures: further studies of their roles in other circumstances are required.     

Characteristics of epilepsy in focal cortical dysplasia in infancy

To describe the poorly known characteristics of epilepsy during infancy in focal cortical dysplasia (FCD), one of the most frequent cause of infantile epilepsy. All 28 patients with FCD referred to two specialized centres were retrospectively studied regarding seizure characteristics, psychomotor evaluation, and response to medical and surgical treatment. All patients presented with early partial seizures. Semiology, but not the age of onset, depended on the topography of the dysplasia, with abnormal eye movements in all cases of posterior FCD. Eleven patients also developed infantile spasms (IS), mainly asymmetrical. IS were easily controlled with Vigabatrin or ACTH, but no partial seizures could be medically controlled except in one patient. All patients except one had abnormal neuropsychological findings. Fifteen patients had surgery, eight became seizure free, and seven were significantly improved regarding psychomotor development. Very early and refractory partial seizures, but easily controlled IS are the main characteristics of FCD in infancy. Only the focal ictal semiology may help differentiate the localization of FCD. Its intrinsic epileptogenicity could sustain this clinical pattern. Since the chances for medical control and normal neurodevelopment are poor, surgical treatment should be considered early in infants with FCD.     

Efficacy and safety of topiramate in infants according to epilepsy syndromes.

Studies of the efficacy of topiramate (TPM) in infants and young children are few. Here we report an open, prospective, and pragmatic study of effectiveness of TPM in terms of epilepsy syndromes, in children aged less than 2 years. The median follow-up period was 11 months. We enrolled 59 children in the study: 22 affected by localization-related epilepsy (LRE), 23 by generalized epilepsy, six by Dravet's syndrome, and eight with unclassifiable epilepsy. TPM was effective (responders showed a decrease of more than 50% in seizure frequency) in 47% of patients, including 13% who were seizure-free at the last visit. TPM was more effective in localization-related epilepsy (48% of responders) than in generalized epilepsy (32% of responders). In the latter group, 19 patients suffered from infantile spasms. Four of six patients with cryptogenic infantile spasms became seizure-free. Of the 13 patients with symptomatic infantile spasms, only one was seizure-free. Results were poor for patients with Dravet's syndrome. In general, TPM was well tolerated. The most frequently reported adverse effects were drowsiness, irritability, hyperthermia, and anorexia. The present study concludes that TPM is effective for a broad range of seizures in infants and young children and represents a valid therapeutic option in this population.     

Convulsive Disorders in the First Year of Life: Neurological and Mental Outcome and Mortality

Mortality and neurological and mental outcome were studied in infants 28 days to 1 year of age with afebrile seizures not due to an acute postnatal injury. Cases were divided into four seizure types: infantile spasms: status epilepticus; and "others" (patients without spasms or status), generalized and partial. Mortality was studied in 334 cases, mental and neurological prognosis in 313 infants followed 1 year or more. Globally the prognosis was very poor even outside cases of infantile spasms. Mortality was higher and mental and neurological sequelae were more common in symptomatic than in cryptogenic cases. The highest mortality and greatest number of neurological defects were in status epilepticus and in "others" partial groups. Severely retarded subjects were more common in infantile spasms and "others" partial. The proportion of mentally normal patients, however, was no different according to ictal type. Mental and neurological prognosis was less unfavorable when the first seizure occurred at or over 6 months. A family history of epilepsy or febrile convulsions (21% of the cases in the whole series) was more common in the "others" subgroups, especially in the cryptogenic "others" (42%). The less unfavorable outcome obtained in cryptogenic "others" generalized with a positive family history.     

Topiramate: efficacy and tolerability in children according to epilepsy syndromes

To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.     

Vigabatrin as Initial Therapy for Infantile Spasms: A European Retrospective Survey

Purpose: The efficacy and tolerability of vigabatrin (VGB) as an add-on therapy in the treatment of infantile spasm (IS) prompted physicians to explore its use as the first drug in this seizure type. Methods: Our retrospective study included 250 infants diagnosed with IS; the data obtained were subjected to peer-group review. Of this infant population, 192 infants were considered to have classic IS and had received VGB as their first treatment for the spasms. There was a slight preponderance of boys (57%) in this population. Mean age of IS onset was 5.8 months; 60% had typical hypsarrhythmia. Results: Initial suppression of spasms was obtained in 68% of infants with a median time to response of 4 days at an average VGB dose of 99 mg/kg/day. The best response was seen in those infants with tuberous sclerosis (96% response) and in those younger than 3 months at onset of spasms (90% response). Of these infants, 43 (22%) of 192 subsequently had other types of seizures, and a recurrence of infantile spasms occurred in 28 (21%) of 131 responders. At the end of this study, 96 of 192 infants who could be evaluated were seizure free with VGB monotherapy. Treatment appeared to be well tolerated, with only 33 (13%) infants with adverse events, of which the most common were somnolence (15 patients) and hyper-kinesia (eight patients). In only two cases did adverse events require VGB withdrawal. Conclusion: This study supports the opinion that VGB may be considered an initial treatment for IS regardless of cause.     

Effect of topiramate on intractable seizures in Taiwanese children

We performed a prospective study to evaluate the effect of topiramate as an adjunctive therapy in Taiwanese children with intractable partial epilepsy and generalized epilepsy. Thirty children aged from 2 to 16 years (8.5 +/- 3.8 years) were enrolled in this study. Eighteen children (60.0%) had partial epilepsy, and 12 children (40.0%) had generalized epilepsy. These children were experiencing more than one seizure per month even under a stable antiepileptic regimen treatment. Topiramate was begun at 1 mg/kg x day, and the dosage was raised by 1 mg/kg x day each week. Titration continued for 4 weeks or more. The maximal dosage was 10 mg/kg x day. In children with partial epilepsy, six children (33.3%) achieved > or = 50% frequency reduction, while eight children (44.4%) achieved a seizure-free state. In children with generalized epilepsy, including infantile spasms, four children (33.3%) achieved > or = 50% frequency reduction, while five children (41.7%) achieved a seizure-free state. The most common adverse effect was poor appetite (10.0%). No idiosyncratic reactions to topiramate were found. Only one patient discontinued topiramate because of central hyperventilation. Topiramate can be used as an adjunctive antiepileptic drug for intractable epileptic children in Taiwan.     

Spectrum of epilepsy in terminal 1p36 deletion syndrome

PURPOSE: Previous reports have summarized the seizures types occurring in 1p36 deletion syndrome. To better define the spectrum of epilepsy, we studied 91 patients (median age 7.8 years) with confirmed 1p36 deletion. METHODS: Based on clinical charts, we retrospectively analyzed the evolution of both the EEG findings and seizures. RESULTS: Epilepsy occurred in 53 patients (58.2%), with onset at a median 2.75 months. First seizures were generalized tonic (8 cases), tonic and clonic (6) or myoclonic (12), simple partial (6), or complex partial (14). Thereafter, 20 patients (21.9%) developed infantile spasms with hypsarrhythmia, at a median age of 5 months. High doses of oral steroids were tried in nine cases, with a prompt remission of seizures in six. Among them, five were seizure-free at the time of evaluation. Conversely, two of three nonresponders to steroids developed severe and refractory epilepsy. At the time of evaluation, 32 patients were seizure-free, from a median age of 1.8 years. Nineteen patients (20.9%) had developed refractory epilepsy with polymorphic seizures, including generalized tonic and tonic-clonic seizures (13) combined with myoclonic seizures (11) and atypical absences (3), atonic seizures (2), or complex partial seizures (3). The EEG showed focal, multifocal or generalized spikes, polyspike, and waves, with poverty of the usual background rhythmic activities. CONCLUSIONS: Early epilepsy is a frequent finding in 1p36 deletion syndrome with infantile spasms as of the most common features that can contribute to a poor clinical outcome. Early diagnosis and management of infantile spasm in this condition is mandatory.     

Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term follow-up study

This study aimed to evaluate the long-term efficacy and safety of topiramate in treating children with drug-resistant epilepsy. A multicentric, retrospective, open-label, add-on study was undertaken of 277 children (mean age 8.4 years; range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy was rated according to the seizure types and epilepsy syndrome. After a mean period of 27.5 months of treatment (range 24-61 months), 11 patients (4%) were seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The efficacy of topiramate treatment was noted in localization-related epilepsy and in generalized epilepsy. In addition, in a group of 114 patients, we compared the initial efficacy (evaluated after a mean of 9 months of follow-up) and the retention at a mean of 30 months of topiramate with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Fifty-five (48%) of 114 patients were initial responders. The retention at a mean of 30 months was 23 of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in patients with generalized epilepsy, such as symptomatic infantile spasms and Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a well-sustained topiramate efficacy was noted among patients with localization-related epilepsy. Globally, adverse events were observed in 161 patients (58%) and were mainly represented by weight loss, hyperthermia, sedation, and nervousness, which, in most cases, disappeared after slowing titration or reducing the dosage of the drug. In conclusion, the present long-term study confirms that topiramate represents a useful drug effective in a wide range of seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that the efficacy of topiramate, when evaluated in the long-term perspective, is more sustained in localization-related epilepsy than in generalized epilepsy.     

The role of vigabatrin in childhood seizure disorders: results from a clinical audit

PURPOSE: The emergence of visual field defects attributed to vigabatrin (VGB) treatment and intramyelinic edema in animal experiments has raised concerns about its future role in the treatment of childhood seizures. METHODS: We evaluated our experience with this antiepileptic agent with retrospective analysis of database and chart audit. RESULTS: Of 73 patients, 43 girls and 33 boys were treated with VGB over a 7-year period. The mean age of patients at the introduction of VGB was 87 months (range, 5-257 months). In 12 of 73 cases, VGB was used as monotherapy; in 61 of 73 cases, it was used as an add-on drug. Seizure types included secondarily generalized seizures (21), mixed seizures (21), partial seizures (18), and generalized seizures (13). Seizure etiology was idiopathic/cryptogenic in 22 patients, symptomatic in 50, and undetermined in a single patient. The mean duration of therapy was 16 months (median, 10 months; range, 1-144 months). VGB was effective in 30 (seven seizure free, 23 with >90% reduction in seizures), partially effective in four (50-90% reduction in seizures), and ineffective in 38 (<50% reduction in seizures). Nearly 50% of patients with infantile spasms responded to VGB. All patients underwent ophthalmic evaluation; two (16%) of 12 patients who could undergo static threshold perimetry were demonstrated to have the characteristic visual field constriction. CONCLUSIONS: VGB is effective in producing a significant reduction in seizure frequency in nearly half the patients with childhood seizures, including refractory epilepsy. Despite emerging concerns regarding visual side effects, this drug retains an important role in the medical management of childhood epilepsy.     

Topiramate in refractory partial-onset seizures in children, adolescents and young adults: a multicentric open trial

PURPOSE: This study was to evaluate the efficacy and safety of topiramate (TPM) in refractory partial epilepsy in children, adolescents and young adults. Methods: We performed a prospective open label add-on study in 55 patients (age 2-30 years, mean 15 years) with refractory partial seizures. Topiramate was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency. RESULTS: TPM was initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24h, up to a maximum daily dose of 12 mg/kg. After 9 months of treatment, 11 patients (20%) had 100% fewer seizures and 25 patients (45%) had a more than 50% seizure reduction. TPM appeared to be effective both in cryptogenic (76.2%) and symptomatic (58.8%) partial epilepsies. Mild to moderate adverse events were present in 25 patients (45.4%), mostly represented by drowsiness, nervousness and hyporexia with or without weight loss. CONCLUSION: TPM was an overall effective and safe add-on drug both in cryptogenic and symptomatic childhood refractory partial seizures, the adverse reactions being generally mild or moderate.     

Effect of topiramate on seizures and respiratory dysrhythmia in Rett syndrome

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.     

托吡酯多中心开放性治疗老年癫痫的临床观察

目的 研究单用或加用托吡酯治疗老年癫痫患者的疗效和不良事件.方法 在一项托吡酯治疗癫痫的多中心开放实验中.对全国52家医院门诊病例的119例60岁以上的老年癫痫患者疗效进行分析.剂量采用8周加量期到200 mg/d,接着是12周的稳定期,治疗期间每月随访一次.结果 稳定期结束后,119例患者中有106例(89.1%)发作减少超过50%.119例患者中65例单用托吡酯治疗.有效率为93.8%,54例合并用药,有效率为83.8%.各种类型癫痫患者单用或加用托吡酯治疗后,发作完全控制的患者的例数均超过50%.单用或加用托吡酯治疗病程分别为小于1年、1～3年、4～6年、大于6年的患者的发作减少频数分别为92.86%、91.67%、100%、94.44%和80.00%、85.71%、70.00%、86.36%.合并用卡马西平、丙戊酸钠、苯妥英钠、苯巴比妥、安定的患者总有效率分别为:79.41%、87.50%、85.71%、0%、80%.单用托吡酯治疗老年患者副作用程度较轻.结论 托吡酯无论单用或加用治疗老年癫痫患者,在稳定期结束后发作次数均明显减少,单用副作用程度较轻.不同的发作类型、基础病程、加用药物对疗效无明显影响.     

Efficacy and tolerability of topiramate in childhood and adolescent epilepsy: a clinical experience.

A 3-year retrospective review was undertaken of the use of topiramate in 51 children aged 3-16 years with partial and generalized epilepsies who attended a tertiary referral epilepsy centre in a large children's hospital. The mean follow-up period was 19 months (range 6-33 months). Twenty-six children (51%) were still receiving topiramate at the time of their last review. Fifteen children (29%) showed a greater than 50% reduction in their seizure frequency and four children (8%) became seizure free, three on topiramate monotherapy. The drug appeared to be most effective in children with moderate learning difficulties with 75% showing an improvement in seizure control compared with 25% of children with normal educational functioning. Topiramate was withdrawn in 25 patients. The reasons for withdrawal included adverse effects in 20, lack of effect in three and worsening of seizures in two patients. Adverse side effects were reported in 57% of the 51 patients. The majority of the side effects were related to behavioural and cognitive difficulties, with less-common side effects including anorexia, weight loss and headaches.