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  1. Article ; Online: Pharmacology and drug interactions of cannabinoids.

    Landmark, Cecilie Johannessen / Brandl, Ulrich

    Epileptic disorders : international epilepsy journal with videotape

    2020  Volume 22, Issue S1, Page(s) 16–22

    Abstract: Cannabinoids include a variety of substances, of which cannabidiol (CBD) is the main substance investigated for the treatment of epilepsy, and this will be the focus in the present review. CBD preparations exist in various forms. There are significant ... ...

    Abstract Cannabinoids include a variety of substances, of which cannabidiol (CBD) is the main substance investigated for the treatment of epilepsy, and this will be the focus in the present review. CBD preparations exist in various forms. There are significant differences in quality control regarding content and reproducibility for an approved drug versus herbal preparations. Cannabidiol has challenging pharmacological properties, and pharmaceutical and pharmacokinetic aspects will depend on the formulation or preparation of a certain product. This article will focus on the characteristics, pharmacokinetic challenges, and interactions of standardised CBD-containing drugs based on evidence from clinical and pharmacokinetic studies.
    MeSH term(s) Anticonvulsants/therapeutic use ; Cannabidiol/pharmacology ; Cannabinoids ; Drug Interactions ; Drug Resistant Epilepsy/drug therapy ; Epilepsy/drug therapy ; Humans ; Lennox Gastaut Syndrome/drug therapy ; Seizures/drug therapy
    Chemical Substances Anticonvulsants ; Cannabinoids ; Cannabidiol (19GBJ60SN5)
    Language English
    Publishing date 2020-01-13
    Publishing country France
    Document type Journal Article
    ZDB-ID 2086797-9
    ISSN 1950-6945 ; 1294-9361
    ISSN (online) 1950-6945
    ISSN 1294-9361
    DOI 10.1684/epd.2019.1123
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  2. Article: Valproate: past, present, and future.

    Johannessen, Cecilie U / Johannessen, Svein I

    CNS drug reviews

    2003  Volume 9, Issue 2, Page(s) 199–216

    Abstract: Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in ... ...

    Abstract Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in excitatory neurotransmission, and modification of monoamines. These mechanisms are discussed in relation to the various clinical uses of the drug. VPA is widely used as an antiepileptic drug with a broad spectrum of activity. In patients, VPA possesses efficacy in the treatment of various epileptic seizures such as absence, myoclonic, and generalized tonic-clonic seizures. It is also effective in the treatment of partial seizures with or without secondary generalization and acutely in status epilepticus. The pharmacokinetic aspects of VPA and the frequent drug interactions between VPA and other drugs are discussed. The available methods for the determination of VPA in body fluids are briefly evaluated. At present, investigations and clinical trials are carried out and evaluated to explore the new indications for VPA in other conditions such as in psychiatric disorders, migraine and neuropathic pain. Furthermore, the toxicity of VPA, both regarding commonly occurring side effects and potential idiosyncratic reactions are described. Derivatives of VPA with improved efficacy and tolerability are in development.
    MeSH term(s) Animals ; Anticonvulsants/chemistry ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Epilepsy/drug therapy ; Humans ; Meta-Analysis as Topic ; Pharmacology, Clinical ; Valproic Acid/analogs & derivatives ; Valproic Acid/chemistry ; Valproic Acid/pharmacology ; Valproic Acid/therapeutic use
    Chemical Substances Anticonvulsants ; Valproic Acid (614OI1Z5WI)
    Language English
    Publishing date 2003-06-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1341919-5
    ISSN 1080-563X
    ISSN 1080-563X
    DOI 10.1111/j.1527-3458.2003.tb00249.x
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  3. Article ; Online: Treatment and challenges with antiepileptic drugs in patients with juvenile myoclonic epilepsy.

    Johannessen Landmark, Cecilie / Fløgstad, Ida / Syvertsen, Marte / Baftiu, Arton / Enger, Ulla / Koht, Jeanette / Johannessen, Svein I

    Epilepsy & behavior : E&B

    2019  Volume 98, Issue Pt A, Page(s) 110–116

    Abstract: Background: Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges.: Method: A ... ...

    Abstract Background: Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges.
    Method: A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007-2018). Additional clinical interviews were performed, and a mixed method approach was applied.
    Results: Ninety patients with defined JME diagnosis, 54/36 women/men aged 14-39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic-clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life.
    Conclusion: Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME.
    MeSH term(s) Adolescent ; Adult ; Anticonvulsants/therapeutic use ; Cohort Studies ; Female ; Humans ; Lamotrigine/therapeutic use ; Levetiracetam/therapeutic use ; Male ; Myoclonic Epilepsy, Juvenile/diagnosis ; Myoclonic Epilepsy, Juvenile/drug therapy ; Myoclonic Epilepsy, Juvenile/epidemiology ; Myoclonus/drug therapy ; Myoclonus/epidemiology ; Myoclonus/psychology ; Norway/epidemiology ; Quality of Life ; Seizures/diagnosis ; Seizures/drug therapy ; Seizures/epidemiology ; Valproic Acid/therapeutic use ; Young Adult
    Chemical Substances Anticonvulsants ; Levetiracetam (44YRR34555) ; Valproic Acid (614OI1Z5WI) ; Lamotrigine (U3H27498KS)
    Language English
    Publishing date 2019-07-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010587-3
    ISSN 1525-5069 ; 1525-5050
    ISSN (online) 1525-5069
    ISSN 1525-5050
    DOI 10.1016/j.yebeh.2019.05.021
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  4. Article ; Online: Long-term follow-up with therapeutic drug monitoring of antiepileptic drugs in patients with juvenile myoclonic epilepsy.

    Johannessen Landmark, Cecilie / Fløgstad, Ida / Baftiu, Arton / Syvertsen, Marte / Enger, Ulla / Koht, Jeanette / Johannessen, Svein I

    Epilepsy research

    2019  Volume 155, Page(s) 106148

    Abstract: Background and purpose: Patients with juvenile myoclonus epilepsy (JME) may experience uncontrolled seizures and challenges regarding adherence. Implementation of therapeutic drug monitoring (TDM) may contribute to individualization of the therapy with ... ...

    Abstract Background and purpose: Patients with juvenile myoclonus epilepsy (JME) may experience uncontrolled seizures and challenges regarding adherence. Implementation of therapeutic drug monitoring (TDM) may contribute to individualization of the therapy with antiepileptic drugs (AEDs). The purpose of this study was to investigate how the treatment of patients with JME is monitored and to demonstrate pharmacokinetic variability within and between patients with a long-term TDM approach.
    Method: Retrospective data from patients with JME from the TDM-database at Drammen Hospital and the National Center for Epilepsy in Norway (2007-2018) were included.
    Results: Data from 80 of 90 patients with JME using AEDs with TDM measurements was included (88%, 49/31 women/men aged 14-39). One third (27, 33%) was seizure free, 19 (24%) had generalized tonic-clonic seizures, and 53 (66%) myoclonic seizures during the last year. The most common AEDs measured included lamotrigine, valproate, and levetiracetam. Long-term TDM demonstrated variability over time expressed as intra-patient median values and inter-patient ranges of 19% (7-47) for valproate, 43% (10-83) for lamotrigine and 35% (6-111) for levetiracetam. Fifteen pecent (83/563) of serum concentrations were below the reference ranges and clould be due to variable adherence. Comedication with valproate for lamotrigine and pregnancy contributed to variability. The applicability is illustrated in a case of 10 years' follow-up in a young woman.
    Conclusion: There was extensive pharmacokinetic variability of AEDs in and between patients with JME. A long-term TDM approach may contribute to closer monitoring of patients with JME and be used as a practical tool during clinical consultations.
    MeSH term(s) Adolescent ; Adult ; Anticonvulsants/therapeutic use ; Drug Monitoring ; Female ; Follow-Up Studies ; Humans ; Lamotrigine/therapeutic use ; Levetiracetam/therapeutic use ; Male ; Medication Adherence ; Myoclonic Epilepsy, Juvenile/drug therapy ; Norway ; Retrospective Studies ; Treatment Outcome ; Valproic Acid/therapeutic use ; Young Adult
    Chemical Substances Anticonvulsants ; Levetiracetam (44YRR34555) ; Valproic Acid (614OI1Z5WI) ; Lamotrigine (U3H27498KS)
    Language English
    Publishing date 2019-05-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 632939-1
    ISSN 1872-6844 ; 0920-1211
    ISSN (online) 1872-6844
    ISSN 0920-1211
    DOI 10.1016/j.eplepsyres.2019.05.016
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    Zs.A 2193: Show issues Location:
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  5. Article ; Online: Is atopic sensitization associated with indicators of early vascular ageing in adolescents?

    Königstein, Karsten / Infanger, Denis / Jacobsen Bertelsen, Randi / Johannessen, Ane / Waje-Andreassen, Ulrike / Schmidt-Trucksäss, Arno / Svanes, Cecilie / Dratva, Julia

    PloS one

    2019  Volume 14, Issue 8, Page(s) e0220198

    Abstract: Background: Chronic systemic inflammation accelerates early vascular ageing. Atopic sensitization and allergic diseases may involve increased inflammatory activity. This study aimed to assess whether atopic sensitization and allergic diseases were ... ...

    Abstract Background: Chronic systemic inflammation accelerates early vascular ageing. Atopic sensitization and allergic diseases may involve increased inflammatory activity. This study aimed to assess whether atopic sensitization and allergic diseases were associated with altered vascular biomarkers in Norwegian adolescents.
    Methods: Distensibility coefficient of the common carotid arteries, carotid intima-media thickness and atopic sensitization (serum total and specific IgEs) were assessed in 95 Norwegian adolescents, who participated in the RHINESSA generation study. Symptoms of allergic disease were assessed by an interviewer-led questionnaire.
    Results: Atopic sensitization was found in 33 (34.7%) of the adolescents. Symptomatic allergic disease was found in 11 (33.3%) of those with atopic sensitization. Distensibility coefficient of the common carotid arteries appeared to be lower in participants with atopic sensitization than in those without (46.99±8.07*10-3/kPa versus 51.50±11.46*10-3/kPa; p>0.05), while carotid intima-media thickness did not differ between these groups (0.50±0.04mm versus 0.50±0.04mm; p>0.05). Crude, as well as age- and sex-adjusted multiple regression, revealed no significant association, neither of atopic sensitization nor of allergic disease, with distensibility coefficient of the common carotid arteries and carotid intima-media thickness.
    Conclusions: Our results do not support the assumption of an adverse impact of atopic sensitization and/or allergic disease on distensibility coefficient of the common carotid arteries and carotid intima-media thickness in Norwegian adolescents. Further research is necessary to study whether the clinical severity of allergic diseases might be more important than the status of allergic disease or atopic sensitization.
    MeSH term(s) Adolescent ; Biomarkers/metabolism ; Blood Vessels/diagnostic imaging ; Blood Vessels/metabolism ; Blood Vessels/physiopathology ; Carotid Intima-Media Thickness ; Female ; Humans ; Hypersensitivity, Immediate/diagnostic imaging ; Hypersensitivity, Immediate/metabolism ; Hypersensitivity, Immediate/physiopathology ; Male ; Surveys and Questionnaires ; Time Factors
    Chemical Substances Biomarkers
    Language English
    Publishing date 2019-08-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0220198
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  6. Article ; Online: Antiepileptic drug withdrawal in juvenile myoclonic epilepsy.

    Syvertsen, Marte / Fløgstad, Ida / Enger, Ulla / Landmark, Cecilie Johannessen / Koht, Jeanette

    Acta neurologica Scandinavica

    2018  Volume 139, Issue 2, Page(s) 192–198

    Abstract: Objectives: Withdrawal of antiepileptic drugs (AEDs) has been discouraged in juvenile myoclonic epilepsy (JME). However, impulsivity as a consequence of executive dysfunction in JME may influence treatment adherence. The aim of the present study was to ... ...

    Abstract Objectives: Withdrawal of antiepileptic drugs (AEDs) has been discouraged in juvenile myoclonic epilepsy (JME). However, impulsivity as a consequence of executive dysfunction in JME may influence treatment adherence. The aim of the present study was to assess how common withdrawal of AEDs is in a large and representative JME group.
    Materials and methods: Patients with genetic generalized epilepsy (GGE) were identified through a retrospective search of medical records at Drammen Hospital, Norway, and invited to a clinical interview. Information related to AED withdrawal was analyzed in those classified as JME.
    Results: A total of 132 patients with GGE were interviewed (87 JME). Thirty-five patients with JME (40%) discontinued AEDs, of which 74% did so without consulting a doctor. The rate of self-withdrawal was significantly higher in JME than in other types of GGE. Having a parent with psychosocial difficulties was significantly over-represented in the JME self-withdrawal group. Twelve of those who discontinued AEDs (34%) were free from generalized tonic-clonic seizures (GTCS) and without antiepileptic drugs >1 year. All but one of them withdrew AEDs without consulting a doctor. Age at first motor seizure was significantly higher in those with a favorable outcome of AED withdrawal.
    Conclusions: Self-withdrawal of AEDs is common in JME, especially in those with troublesome conditions at home. However, about 1/3 may remain free from GTCS without AEDs. The findings indicate a need for a stronger follow-up with appropriate information about the prognosis of the disorder.
    MeSH term(s) Adolescent ; Adult ; Anticonvulsants/administration & dosage ; Anticonvulsants/adverse effects ; Anticonvulsants/therapeutic use ; Drug Administration Schedule ; Female ; Humans ; Male ; Myoclonic Epilepsy, Juvenile/drug therapy
    Chemical Substances Anticonvulsants
    Language English
    Publishing date 2018-11-15
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 90-5
    ISSN 1600-0404 ; 0001-6314
    ISSN (online) 1600-0404
    ISSN 0001-6314
    DOI 10.1111/ane.13042
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    Ui I Zs.142: Show issues Location:
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  7. Article ; Online: Epilepsy and cannabidiol: a guide to treatment.

    Arzimanoglou, Alexis / Brandl, Ulrich / Cross, J Helen / Gil-Nagel, Antonio / Lagae, Lieven / Landmark, Cecilie Johannessen / Specchio, Nicola / Nabbout, Rima / Thiele, Elizabeth A / Gubbay, Oliver / The Cannabinoids International Experts Panel

    Epileptic disorders : international epilepsy journal with videotape

    2020  Volume 22, Issue 1, Page(s) 1–14

    Abstract: The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the ... ...

    Abstract The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market. The effects of these products are fundamentally dependent on the purity, preparation, and concentration of CBD and other components, and consensus and standardisation are severely lacking regarding their preparation, composition, usage and effectiveness. This review aims to provide information to neurologists and epileptologists on the therapeutic value of CBD products, principally a purified form, in routine practice for patients with intractable epilepsy.
    MeSH term(s) Cannabidiol/administration & dosage ; Cannabidiol/pharmacology ; Cannabidiol/standards ; Cannabinoid Receptor Modulators/administration & dosage ; Cannabinoid Receptor Modulators/pharmacology ; Cannabinoid Receptor Modulators/standards ; Drug Resistant Epilepsy/drug therapy ; Epilepsies, Myoclonic/drug therapy ; Humans ; Lennox Gastaut Syndrome/drug therapy ; Practice Guidelines as Topic
    Chemical Substances Cannabinoid Receptor Modulators ; Cannabidiol (19GBJ60SN5)
    Language English
    Publishing date 2020-02-25
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 2086797-9
    ISSN 1950-6945 ; 1294-9361
    ISSN (online) 1950-6945
    ISSN 1294-9361
    DOI 10.1684/epd.2020.1141
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