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Central Nervous System (CNS) disorders pose a major threat to the quality of life. They are complex in their mode of causing disturbances to mental stability, behavior and overall psychological well being. The chemistry of these disorders is interlinked with a spectrum of pathways. Treatment approaches targeted at the management of these disorders are important to consider and need thorough understanding with regard to their safety, efficacy and many other aspects. The present description is concerned with highlighting the treatment strategies of Lithium and Lamotrigine drugs for bipolar affective disorders. A bipolar disorder is a disease where individuals often switch between depression and bad or good moods. These swings in mood between depression and mania are very rapid. Bioloar disorder is of two types Type 1 and type 2.Individuals with type I disorder, earlier known as manic depression, posses minimum one episode of mania and major depression periods. Individuals with type II disorder,II have do not possess complete mania. They have increased impulsiveness and levels in energy that are similar to hypomania in the degree of severity. The periods related to type II alternate with depression episodes.
Firstly, there is a need to know about the role of mood stabilizers in psychiatry.
Mood stabilizer is a substance used for curing depressive symptoms and acute manic symptoms. They are also used in prophylactic measure for managing bipolar disorder‘s depressive and manic symptoms.In detail, mood disorders are conventionally considered as neurochemical disorders. these are linked with alterations in cellular resilience and structural plasticity. So in CNS, the role of mood stabilizers is to enhance the cytoprotective protein bcl-2 expression in the human neuronal cells and in vivo.
Here, mood stabilizers stimulate a pathway of signaling used by mitogen activated protein (MAP) kinase and extracellular signal-regulated kinase (ERK) pathway which are used by growth factors of internal origin. In addition, they enable the trophic help required for improving and managing ordinary synaptic connections. They also facilitate the chemical signals to restabilize the maximum output of vital circuits needed for general significance. Earlier, the role of mood stabilizing agents was better implicated in lessening the mood disorder led morbidity and mortality. This was accomplished by studying the gene expressin patterns of important kinases like protein kinase C (PKC) alpha. Preventing the activity of PKC is essential in contributing to antimanic strategy through the administration of mood-stabilizing agents.
Treatment options vary for Bipolar disorders. They may be biological treatment, with the use of mood stabilizers like drugs which have long been employed or psychological and social treatment with cognitive behavior therapy. Among these options, there is a need to choose and consider more effective therapy which has become an issue for health care professionals. Practice guidelines and clinical consensus support the use of mood stabilizers such as lithium or anticonvulsants either as add-on therapy for monotherapy for bipolar depression.5 But lithium was described to be efficacious in the reduction of manic relapses, and is not efficacious in the reduction of relapses that lead to depression. Lamotrigine, an anticonvulsant does not possess antimanic properties and not as efficacious for major depressive disorder treatment even though for bipolar depression, it is a sufficient antidepressant.In the period of 80s, etiological theories have been propounded for mental disorders which focus on psychological components of risk and susceptibility. On these grounds, cognitive therapy has gained popularity as adjunct for treating individuals with depressive disorders of severe and chronic nature.Being the coherent model as the solid framework, cognitive therapy is considered as highly effective psychological treatment strategy. It gives the patient a clear picture on the reasons behind the strategy employed, contributes to patients utilization of learned skills, improves the patients’ self-and efficacy sense. So cognitive therapy is considered as efficacious approach in the bipolar disorder treatment.Very often bipolar disorder patients face resistance to depression treatment approaches which is known as Treatment Resistant Depression (TRD). These patients even though have social functioning alterations, psychosocial treatment was largely investigated to prove its efficacy.
To this end, drug therapy was combined with cognitive behavioral therapy (group-CBT) to determine if such approach could enhance both social interactions and symptoms of depression in patients with TRD presented in mild form. CBT approach corrected dysfunctional cognitions, dysfunctional cognitions and psychosocial functioning. This has indicated that medication when being added with CBT has led to a positive effect in treatment resistance patients.
Earlier, when discriminated with psychoeducational principle based cognitive-behavioural therapy (CBT), there was no proper assessment of bipolar disorder’s psychosocial investigations with regard to psychoeducation (PE).Patients who received optimized treatment of BD,CBT approach as an additional support or adjunct in the longer course might be beneficial rather than PE implemented in short course.
These studies indicate that psychological treatment appears to be more effective than the biological treatment provided when it is given as an adjunct compared to biological treatment approaches.However, the use of lithium and Lamotrigine do have some benefits if one precisely considers their safety and efficacy. Lithium also known as Lithobid or Eskalith is bipolar disorder prescription drug. It is regarded as “maintenance treatment to support avoiding depression or mania episodes. Its indications include Depression, agitation not related bipolar disorder, Migraine, chemotherapy induced Neutropenia, Graves’ disease etc. The CNS effects of lithium toxicity carry the highest morbidity. They begin when present in mild form from sedation irritation to delirium, seizures, and death in severe cases. In overdoses of 1.6mEq/L,ut, of serum lithium levels,severe neurotoxicity results. It also causes life threatening effects like thyroid and renal toxicity, teratogenic disturbances etc. Lithium interacts much with diurectics and moderately with Non-steroidal anti-inflammatory drugs (NSAIDs) that cause toxicity. Lithium compliance is based on once daily dosing which was rated the most at 79% compared to twice , thrice and four times. It s contraindications are pregnancy, drug hypersensitivity, elderly patyients, caution if the patient has febrile illness, renal impairment, and volume depletion. Lithium monitoring parameters include diuretic or ACE inhibitor usage, depleted Na, baseline analysis of urine, Cr, dehydration etc. Next, Lamotrigine is indicated for Lennox-Gastaut syndrome generalized seizures and partial seizures in epilepsy as an adjunct.It is recommended for depression and bipolar I disorder as maintenance drug. The toxicity of lamotrigine is linked with epilepsy patients who were found with high concentrations of serum lamotrigine when prescribed. But later this toxic effect was not proven to be much significant from clinical trials. Lamotrigine interacts mostly with other drug valproate/ valproic acid and leads to rash which may be life threatening due to high dosage levels. The compliance of lamotrigine is based on valproate’s absence for its instant release and is recommended once daily.Its contraindications are drug hypersensitivity, caution in pregnant women, those on risk of suicide, hepatic and renal alterations. The above information reflects more toxic risk of lithium compared to Lamotrigine.
From a study, it was reported that compared to compared to lithium in the bipolar depression treatment, Lamotrigine was reported to be more safe and efficacious. In older patients with Bipolar I depression, the tolerability and efficacy of mood stabilizers has been investigated. Both lithium and lamotrigine were found to execute good tolerance and effective in maintenance. Lamotrigine has leas t side effects like headache, backache and rash whereas Lithium has most severe side effects like fatigue, diarrhea, xerostomia, headache and dyspraxia. However, even though both are suited well for treating older patients, it is reasonable to mention that Lamotrigine has overall safety and efficacy with regard to the safety, low toxicity and minimum drug interaction. With the above information, it can be summarized that the 74 year old lady with 38 years history of BAD, low mood and suicide attempt as associated complications needs a precise monitoring. Especially, Lamotrigine when used with
Quetiapine Procyclidine may not contribute to any side effects. But blood indices need to monitored regularly.These may involve counts of red blood cell. White blood cell, monocuyte or lymphocyte. The intercellular levels of Lamotrigine when used with other drugs in the old patient may induce some sort of changes in the blood indices which are essential parameters to consider. A failure to assess the blood indices may lead to improper management of Bipolar disorder with regard to drug interactions.This could avoid any chances of recurrences in the episodes of maniac symptoms or depression that could become aggravated with the increasing age.
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Matsunaga M, Okamoto Y, Suzuki S, Kinoshita A, Yoshimura S, Yoshino A, Kunisato Y, Yamawaki S. Psychosocial functioning in patients with Treatment-Resistant Depression after group cognitive behavioral therapy.BMC Psychiatry. 2010; 10:22.
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