Most Effective Depression Treatments

Destroy Depression

Destroy Depression is written by James Gordon, a former sufferer of depression from the United Kingdom who was unhappy with the treatment he was being given by medical personnell to fight his illness. Apparently, he stopped All of his medication one day and began to search for answers on how to cure himself of depression in a 100% natural way. He spent every waking hour researching all he could on the subject, making notes and changing things along the way until he had totally cured his depression. Three years later, he put all of his findings into an eBook and the Destroy Depression System was born. The Destroy Depression System is a comprehensive system that will guide you to overcome your depression and to prevent it from injuring you mentally and physically. Read more here...

Destroy Depression Summary

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Interictal Depressive Episodes

Interictal depressive episodes disorders are the most frequent form of depression and, by the same token, the most frequent psychiatric co-morbidity in PWE, with prevalence rates ranging from 11 to 60 7 . They may mimic major depression, dysthymic, minor depressive and bipolar disorders described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). In a significant number of patients, however, depression may present with atypical clinical characteristics. In primary depressive disorders, the difference between major depression and dysthymic disorder is based largely on severity, persistence and chronicity. According to DSM-IV criteria, symptoms in both disorders may include combinations of depressed mood, anhedonia, feelings of worthlessness and guilt, decreased ability to concentrate, recurrent thoughts of death and neurovegetative symptoms (i.e. weight loss or gain, insomnia or hypersomnia, psychomotor agitation or retardation and fatigue). The...

Identifying Depressed Patients In The Neurologists Office

Inquiry of anhedonia, that is the inability to find pleasure in most activities, is the simplest way of suspecting the existence of a depressive disorder. Second, the use of self-rating screening instruments can be of great assistance. A six-item screening instrument, the neurological disorders depression inventory for epilepsy (NDDI-E), was recently validated to screen for major depressive episodes in patients with epilepsy 14 . This instrument has the advantage of being constructed specifically to minimize confounding factors that plague other instruments, such as adverse events related to anti-epileptic drugs (AEDs) or cognitive problems associated with epilepsy. Completion of the instrument takes less than 3 min. A score of 14 or higher is suggestive of a major depressive episode and indicates that a more in-depth evaluation is necessary. Other self-rating screening instruments developed to identify symptoms of depression in the general population, such as the Beck Depression...

Therapeutic expectations of pharmacotherapy of depressive disorders

A major depressive episode left untreated may last between 6 and 24 months in 90-95 of cases while the remaining 5-10 could last more than 2 years. Two-thirds of patients are expected to 'respond' to anti-depressant medication and in controlled studies, one-third are expected to respond to placebo. Approximately 15-20 of patients will fail to respond to any anti-depressant trial. It is estimated that approximately 50 of patients will reach remission within the first 6 months and about two-thirds within 2 years of the start of therapy. The pharmacological treatment of major depressive episodes can be divided into three phases 2 A continuation phase, which spans the 12th and 52nd weeks, and which aims to prevent the recurrence of a depressive episode. The anti-depressant medication must be maintained at the same dose. 3 A maintenance phase, which aims to maintain the patient in a euthymic state indefinitely. Its duration depends on the number of prior major depressive episodes. As...

Major Depression

A diagnosis of major depressive disorder can be made after a single or multiple major depressive episodes. Establishment of whether the depressive episode is the first to occur is of utmost importance as the risk of subsequent major depressive episodes is of 50 after a single episode, 70 after two episodes and almost 100 after more than two episodes 8 . Ten to 15 years after an index major depressive episode, about 80-90 of patients can be expected to have a recurrence. Patients with dysthymic and minor depressive disorders will often experience one or recurrent major depressive episodes. This is referred to as 'double depression'. Furthermore, recent studies have highlighted the importance of also recognizing sub-syndromal forms of depression, as these are associated with a risk of developing a major depressive episode

Examination And Investigations

The patient was admitted to the Epilepsy Center of the University of Bonn, Germany, 9 months after her initial seizure. Physical examination revealed no focal neurological deficits. She had severe affective abnormalities, consisting of major depression with lability of mood. Neuropsychological testing revealed verbal and visual memory deficits.

Preventing suicide in epilepsy

Preventing suicide in epilepsy patients consists of effectively treating both the dysphoric disorder and the psychosis of the interictal phase (Blumer, 1997 Blumer et al., 2000 Blumer and Zielinski, 1988). We now treat both the patients with suicidal dysphoric moods and those with interictal psychoses with double antidepress-ant medication, enhanced if necessary with an atypical neuroleptic drug, e.g. with the combination of 100-150 mg imipramine, 20-40 mg paroxetine and 2-4 mg risperidone daily. The same treatment has been effective for patients with severe postictal depressive mood, although we have not had the occasion to treat a patient with ictal depression and suicidal intensity of the postictal phase. The dysphoric disorder is endogenous, and psychotherapy without pharmacotherapy leaves the patient with suicidal moods at risk. The bias against using antidepressants for the psychiatric disorders of epilepsy on the grounds that they may lower the seizure threshold (McConnell and...

Frontal lobe and behaviour disorders

The finding of antisocial and aggressive behaviour with frontal lobe damage is not in itself new. A prominent and often cited example is the historic case of Phineas Gage, who after an accident with a severe frontal brain injury changed from a well-mannered man into an irresponsible and convention-neglecting person (Damasio et al., 1994 Harlow, 1868). New in the study of Anderson et al. (1999) is the finding that whether patients not only display severe behavioural disorders but also fail to see the moral of the behaviour depends on the age at the lesion onset (Dolan, 1999). Consequently, the orbito-frontal cortex seems not only important for behaviour control but also for the acquisition of social and interpersonal rules. It is important to note that irresponsible, aggressive and sociopathic behaviours can occur independent of intellectual abilities, which are often well preserved in frontal lesions. Other areas in which the orbital and medial prefrontal cortex are believed to play a...

Treatment and outcome

I counseled her mother on the typical benign prognosis of absence epilepsy, and started the patient on valproate. Her spells improved for a few weeks, but then relapsed. She was having three to 12 events a day. Ethosuximide was added she again improved for a few weeks but then regressed again. She developed a sleep disturbance with restlessness, squirming and hallucinations. Ethosuximide was discontinued and her symptoms improved. A few months later, she was having dozens of seizures a day. A repeat trial of ethosuximide improved her symptoms but was associated with stomach upset and vomiting. She developed behavioral problems with uncharacteristically whiny and sometimes aggressive behavior. This improved when valproate was stopped and clonazepam was added. However, clonazepam was associated with behavioral side effects including crying and mood swings, and it was discontinued after a brief trial. She was having up to 20 absence spells a day.

Depression and anxiety

Conventional mood disorders are encountered in many patients with epilepsy, and these include anxiety, depression, dysthymia and panic disorders. Intermittent affective-somatoform symptoms are frequently present in chronic epilepsy and include irritability, depressive moods, anergia, insomnia, atypical pains, anxiety, phobic fears and euphoric moods. Some are present continually but others show marked variation in relation to seizure activity. Prodromal and peri-ictal dysphoria are common. Both depression and anxiety in epilepsy respond to conventional antidepressant drugs. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are routinely given. Fluoxetine is a widely prescribed drug, although it is a powerful CYP3A4 inhibitor and can interact with carbamazepine and other antiepileptics. Other SSRIs commonly used in patients with epilepsy include paroxe-tine and citalopram. Paroxetine does not interact with common antiepileptic drugs. Citalopram may be...

Psychiatric disturbance and personality change after epilepsy surgery

Epilepsy surgery carries a risk of precipitating psychiatric disturbance. The most common problems are mood swings, anxiety and depression. These are seen in 20-30 of people who undergo surgery for epilepsy. Although distressing, these are generally mild and remit within weeks or months, although some people may need antidepressant medication or counselling.

Depression and epilepsy an overview

Assessing the frequency of epilepsy and depression from selected clinic samples gives a bias toward the more severely affected patients and also those on the most medication. A better understanding of comorbid psychopathology should come from community studies. Edeh and Toone (1987) carried out a general practice study in the United Kingdom and reported that 22 of unselected patients with epilepsy were rated as having a depressive disorder. A Canadian Community Health Survey examined 253 people with epilepsy using a rating scale to identify a history of depression, and noted a lifetime prevalence of depression at 22 this was compared with 12 in the general population (Tellez-Zenteno et at, 2005). There are a number of studies from selected patient groups, for example tertiary centers, or from those awaiting surgery for epilepsy, which note in these populations an even higher frequency of depression. Victoroff et al. (1994) evaluated 60 patients with intractable complex partial...

The relationship of epilepsy syndromes to depression

Seizures, and they also are more likely to be taking more extensive medication than those with non-temporal epilepsy, and they may be at increased risk. Thus, some studies have shown patients with temporal lobe epilepsy to be more prone to depression than other groups, but other investigations have failed to confirm this. Examining etiology of epilepsy, Quiske et al. (2000) found that patients with temporal lobe epilepsy who had mesial temporal sclerosis were more likely to report depression. In general terms, there is more agreement that patients with complex partial seizures are more likely to have a depressive disorder (Robertson, 1998).

Mental Health of Adults with Epilepsy

Summary Mental Health of Adults With Epilepsy, a chapter in Epilepsy Patient and Family Guide, discusses the mental and behavioral aspects of epilepsy in adult patients. Behavioral disturbances in people with epilepsy may be unrelated to epilepsy, or related to the person's emotional reactions to having epilepsy, the effect of medications, or epilepsy. The chapter discusses (1) personality and epilepsy, (2) depression in epilepsy and in the general population, (3) causes of depression in people with epilepsy, (4) treating depression, (5) anxiety disorders in patients with epilepsy and in the general population, (6)

The relationship of antiepileptic drugs AEDs to depression

The role of AEDs in precipitating depression has become of considerable interest following the introduction of a spectrum of molecules referred to as new AEDs (Mula and Sander, 2007). Within this literature the concept of forced normalization has been revived the phenomenon which describes the sudden switching off of seizures in people with intractable epilepsy who then develop an alternative psychiatric syndrome. Very often this is a psychotic disorder, but depressive symptoms are also reported (Trimble, 1998). This literature is of interest

Bipolar disorder and epilepsy

These data raise some doubts about the previous suggestions that bipolar disorder is rare in people with epilepsy, and raise doubts as to our knowledge of the association between these two disorders. The older discussions related more to classical manic-depressive disorder, as opposed to the concept of the bipolar spectrum, which is currently the focus of psychiatric interest. However, it is clearly

Side Effects That Imitate Seizures

Her past medical history included minor surgeries, two uneventful pregnancies with normal children, and the occasional treatment of depression with tricyclic antidepressants. There was no history of head trauma, febrile seizures or previous hospitalization. Prior medications included divalproex, phenytoin, felbamate, gabapentin and lamotrigine. Each was unsuccessful in stopping her seizures and several had significant cognitive effects.

Is There An Epilepsyspecific Affective Syndrome

The comorbidity between mood and anxiety disorders could be a potential example of such a peculiarity (see Chapter 16). Comorbid anxiety symptoms have been identified in 73 of patients with epilepsy and depression (Robertson et al., 1987 , Jones et al., 2005a). However, it is still unknown whether this is an association identical to that described in primary mood disorders or a comorbidity typical of chronic illnesses (where anxiety is present, with irritability and generalized turmoil), or if it is distinctive only of epilepsy and interlinked with the underlying brain pathology. The recognition of comorbid anxiety symptoms is very important clinically, since they may worsen the quality of life of depressed patients and significantly increase the risk of suicide (Kanner, 2006). has unique manifestations that are poorly reflected by conventional classification systems such as DSM-IV and ICD-10 (Krishnamoorthy et al., 2007) . Mendez et al. (1986) investigated the clinical semiology of...

Psychiatric side effects of new antiepileptic drugs

Batrin, a London group had published an incidence of significant psychiatric complications in 7 of treated patients (Sander et al., 1991). Thomas et al. (1996) have analysed case records of psychiatric complications, episodes of psychoses or major depression, reported to the manufacturer of vigabatrin. With respect to psychoses the authors identified three patterns of a total of 28 psychotic patients, eleven had become seizure free with vigabatrin, six had a postictal psychosis following a cluster of seizures after initial seizure control, possibly related to tolerance, and two psychoses occurred after withdrawal of vigabatrin. Psychiatric side effects are not restricted to patients with complicated epilepsies who receive vigabatrin as an add-on treatment. The monotherapy trials showed a significantly increased incidence of depressive disorders in 5 of vigabatrin-treated patients as compared to only 1 in a carbamazepine-treated group (Chadwick, 1999).

Shared Neurotransmitter Abnormalities In Depression And Epilepsy

Both depression and epilepsy have been linked to the abnormal activity of several neurotransmitters, including serotonin (5-hydroxytryptamine, 5-HT), norepineph-rine (NE), dopamine (DA), y-aminobutyric acid (GABA), and glutamate (Ressler and Nemeroff, 2000 Nemeroff and Owens, 2002 Nestler et al., 2002 Jobe, 2003). Neurotransmitter abnormalities in depression form the theoretical basis for psy-chopharmacologic treatment with monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) as well as for the use of psychoactive AEDs such as valproic acid (VPA), carbamazepine (CBZ), oxcarbaze-pine (OXC), and lamotrigine (LTG) in the treatment of mood disorders.

The Treatment Of Patients With Epilepsy And Depression

Several factors may contribute to the underrecognition of depression in epilepsy and lack of adequate therapeutic intervention. These may include the failure to appreciate the impact of depression on quality of life (Wiegartz et al., 1999 Gilliam, 2002) , concerns over the epileptogenic potential of the antidepressants Widespread concern in regards to the potential for antidepressants to worsen seizures appears to be mostly unsubstantiated. There are no reports in the literature of TCA-induced seizures at therapeutic serum levels. Patients who suffered seizures at therapeutic doses were discovered to be slow metabolizers of the drug. Rapid increases in medication, an abnormal EEG, the presence of CNS pathology, and personal and family history of epilepsy were other risk factors for developing seizures in non-epileptic patients (Kanner, 2003a). The actual risk of causing seizures to worsen in patients with epilepsy by the use of antidepressant medications appears to be low. In a...

How could the development of personality disorders and their neuronal basis be explained

Now to the postoperative psychiatric situation she had a severe major depression starting shortly after surgery. The use of antidepressants was limited because she refused to take them after only a few days. She had massive feelings of disgust concerning her husband. About half a year after surgery she recovered from her depression, but then started to throw all conventions overboard and showed manic symptoms. Within the following months she developed the delusional idea of having a love-affair with a neurologist at our centre. She went from manic symptoms to paranoid-hallucinatory experiences of being influenced through the internet in her thoughts and emotions. She left her home and was recently hospitalized against her will and put on neuroleptic drugs.

VNS as an antidepressant treatment in nonepileptic patients

From the evidence reported above it is a small step to the evaluation of VNS for treatment of clinical depressions in nonepileptic patients. Recently, Rush et al. (2000) published their findings from a first single-arm study on this issue. On the basis of ethical considerations, only the most affected patients from different clinics in Dallas were included and provided with a vagus nerve stimulator (n 30). Inclusion criteria were a DSM-IV diagnosis of major depression disorder (MDD), bipolar I or bipolar II disorder (American Psychiatric Association, 1994). Patients had to be in a major depressive episode (MDE) which either was lasting 2 years or which was one of at least four MDEs during life. Finally, they had to have failed on at least two antidepressant medication treatments from different medication groups during the current MDE. sample size these findings are intriguing and justify further investigations. From a clinical point of view, these data raise hope for a totally new...

Epidemiology Of Depression And Anxiety In Epilepsy

Depression is believed to be the most common psychiatric disorder among individuals with epilepsy (Hermann et al., 2000 Kanner, 2003) . For centuries a link between epilepsy and depression was hypothesized. A poignant example is evidenced by the Hippocratic corpus written around 400 BC. It stated melancholics ordinarily become epileptics and epileptics melancholics (Lewis, 1934). More recently, Hesdorffer et al. (2000) found that individuals with epilepsy were 3.7 times more likely to have a depressive episode prior to the first seizure. In a study in Iceland among children and adults with epilepsy, similar results were reported, revealing individuals with epilepsy were 1.7 times more likely to have a history of major depression prior to the first unprovoked seizure (Hesdorffer et al.) 2006). Depression appears to be a risk factor for the onset of seizures, and depression appears to be a significant comorbidity after the seizure disorder is diagnosed. There continues to be some...

Depression And Anxiety In Epilepsy What Do We Know

Several recent population-based studies have reported elevated symptoms of depression and anxiety among adults and children with epilepsy (Davies et al. 2003 Strine et al. 2005 Tellez-Zenteno et al. 2005 Kobau et al. 2006). However, in the epilepsy literature the co-occurrence of depression and anxiety has received limited attention. Depression and anxiety disorders are frequently reported in over arching categories (e.g., internalizing disorder, neurosis) with no ability to distinguish the individual prevalence rates of each disorder (Jacoby et al. 1996 Davies et al. 2003 Strine et al. 2003), or depression and anxiety are reported as distinct disorders with no acknowledgement of co-occurrence (Ring et al. 1998 Glosser et al. 2000) . Recently, in the 2004 HealthStyles Survey, a large population-based mail survey, Kobau et al. (2006) found 16.7 (OR 3.2 95 CI 1.4-7.4) of individuals with active epilepsy reported both depression and anxiety during the past year. In a multicenter study,...

Atypical Clinical Manifestations Of Depression In Epilepsy

As stated above, PWE may often experience depressive disorders that do not meet any Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria or may present symptoms of depression intermittently on what is considered today as a sub-syndromal form of depression. In one study that used Diagnostic and Statistical Manual of Mental Disorders, Third edition Revised (DSM-III-R) criteria, 50 of depressive disorders had to be classified as atypical depression 10 , while this occurred in 25 of depressive disorders in a separate study that used DSM-IV criteria 11 . In a review of the literature, Blumer and Altshuler concluded that the atypical clinical expressions of depression are relatively frequent in PWE 12 . These episodes are more likely to resemble a dysthymic disorder, with respect to the symptom severity in these forms of depression, symptoms last for periods ranging between several hours and several days that are interrupted by symptom-free periods of similar duration....

Common Symptomatology In Depression And Anxiety

Depression and anxiety disorders have overlapping symptomatology. As defined by the DSM-IV-TR (American Psychiatric Association, 2000), major depression and generalized anxiety disorder share four diagnostic symptoms, which include sleep disturbance, difficulty concentrating, restlessness and fatigue. In the DSM-III all anxiety disorders (i.e., social phobia, panic disorder, etc.) were required to occur independently of and symptoms were to be present separate from a depressive episode. However, in the DSM-IIIR (American Psychiatric Association, 1987) this hierarchy was eliminated for all anxiety disorders except generalized anxiety disorder (Zimmerman and Chelminski, 2003). The diagnostic criteria for generalized anxiety disorder states that criteria must be reached independently and outside the presence of a depressive disorder, and this exception is likely related to the fact that both disorders have overlapping symptoms (Zimmermann and Chelminski, 2003 DSM-IV-TR, 2000)....

Pharmacotherapy Of Depression In Epilepsy

Today, anti-depressant drugs of the families of the SSRIs and of the selective norepinephrine reuptake inhibitors (SNRIs) have become the first line of pharmacotherapy for primary major, dysthymic and minor depressive disorders. Fortunately, these drugs We must keep in mind, however, that the data available for the management of mood disorders in PWE are derived from open trials, based on the experience obtained in the treatment of primary depression disorders. Indeed, to date there has been only one controlled study published in the literature that compared under blind conditions the efficacy of two anti-depressant drugs (amitriptyline and mianserin) with placebo in major depression of PWE 16 .

Do Antidepressant Drugs Worsen Seizures

There is a widespread concern among clinicians that anti-depressant drugs can worsen seizures such a worry is one of the more frequent causes that has limited the prescription of these drugs in PWE who suffer from a depressive disorder. Yet, a careful review of the literature shows that in the general population, an anti-depressant-related increased risk of epileptic seizures has been limited to four anti-depressant drugs clomipramine, maprotiline, amoxepine and bupropion, and to tricyclic anti-depressant drugs at high plasma serum concentrations resulting from overdoses or encountered in individuals with a genetic predisposition to be a slow metabolizer. In animal models of epilepsy, anti-depressant drugs that increase the synaptic concentration of serotonin and epinephrine have been found to have anti-convulsant properties. A recent study appears to confirm a 'protective' effect of SSRIs and SNRIs in depressed patients Alper et al. compared the incidence of seizures between...

Pharmacokinetic interactions

The interactions between antipsychotic drugs and antiepileptic drugs have been even less studied than the antidepressants. Some psychotropics, such as haloperi-dol, mainly metabolize using the P450 system, others such as chlorpromazine use different liver mechanisms. However, decreases in the levels of some neuroleptics can occur in patients prescribed anticonvulsant drugs, and several studies have been carried out in patients with schizophrenia who have received both carbamaz-epine and a neuroleptic. Haloperidol levels can drop by up to 50 following coadministration of the antiepileptic (Arana et al., 1986). Clozapine and olanzapine primarily use the CYP1A2 isoenzyme, which may lead to interactions with some of the tricyclic antidepressants, and carbamazepine.

The Use Of Aeds In The Treatment Of Mood Disorders In Pwe

The use of an AED with mood-stabilizing properties (if the patient is not taking one already) such as carbamazepine, oxcarbazepine, valproic acid and lamotrigine, can be an alternative strategy to a continuation of the anti-depressant drugs during the maintenance phase. These AEDs are known to have a prophylactic effect against the recurrence of depressive and manic episodes in primary mood disorders, but in mood disorders of PWE, this prophylactic effect has yet to be established. This point is particularly relevant in the management of atypical depressive disorders.

Aeds Have Many Distinct Cellular Mechanisms Of Action

The other agents, including valproate, topiramate and levetiracetam, have broader utility. With very few exceptions, each AED acts in a mechanistically distinct way. This is not the situation in other therapeutic areas. For example, the triptans used to abort migraine attacks all act in a similar fashion as agonists of serotonin 5-HTj B and 5-HTjd receptors the selective serotonin reuptake inhibitors used to treat depression all block the serotonin transporter the many statins are all HMG-CoA reductase inhibitors and the proton pump inhibitors all have the same molecular target. In contrast, each AED generally acts on a unique set of molecular targets. Even when they share the same molecular target, as is the case for AEDs that act on voltage-activated sodium channels, the biophysical details for each drug are sufficiently different that the mechanisms must be considered distinct.1 For example, there may be important differences in binding rate, binding affinity,2 the ability to block...

Mood Disorders That Should Be Managed By Psychiatrists From The Onset

Given their relatively high prevalence in PWE, neurologists should be able to identify the depressive and bipolar disorders described above. They should know how to initiate pharmacotherapy for major, dysthymic and minor depressive episodes. Thus, in which type of depressive disorders can a neurologist start pharmacotherapy and when should patients be referred from the start to the care of a psychiatrist The following are the mood disorders that deserve immediate referral to a psychiatrist. Any Depressive Episode Associated with Suicidal Ideation Any Major Depressive Disorder with Psychotic Features Approximately 25 of major depressive disorders can present with psychotic features. In such cases, pharmacotherapy has to include anti-psychotic and anti-depressant drugs and at times, the use of electroshock therapy has to be considered. Furthermore, the presence of psychotic symptomatology increases significantly the suicidal risk of these patients. Thus, these patients need to be placed...

Interictal Anxiety Disorders

As stated above, PD and GAD are commonly associated with depressive disorders and their presence conveys an increased suicidal risk. Thus, when the primary complaint is that of an anxiety disorder, clinicians must carefully investigate the presence of depressive symptoms or episodes. GAD consists of constant uncontrollable worry on a daily basis of at least 6 months' duration that is associated with at least three of the following six symptoms restlessness, easy fatiguability, decreased concentration, irritability, muscle tension and sleep disturbances. Given the frequent confusion between ictal and interictal panic, the differences between the two will be discussed in greater detail in the next section.

Learning disability behavioural disorder and psychosis

The presence of a chronic interictal psychosis is also generally a contra-indication to surgery, as the psychosis can worsen dramatically after surgery. Decisions about surgical treatment should not be made by severely depressed patients. Psychosis and depression may also prevent informed consent. Again, individual decisions in this situation require a detailed assessment by an experienced practitioner.

Discussion And Implications

There are a number of implications for future research. First and importantly, we must begin to aggressively study treatment options, both pharmacological and psychotherapeutic, in order to reduce the negative impact of the disorders on the lives of individuals with epilepsy. Second, we must continue to conduct neuroana-tomical studies to obtain more knowledge about the neurobiological link between epilepsy, anxiety, and depression. Third, we must continue to explore the neuro-pathogenic mechanisms of all three disorders, and the potential implications of the dynamic relationship on the expression of these disorders. This knowledge could inform the development of medications to treat depression, anxiety, and epilepsy. Finally, it will be important to identify environmental and psychosocial risk factors for anxiety and depression. It is clear that neurobiological and genetic mechanisms are influenced by environmental factors and their expression is based on exposure to particular...

Psychotherapeutic Interventions

Despite awareness of the efficacy of psychotherapeutic interventions for depression and anxiety, they have rarely been studied in epilepsy. In a recent Cochrane review of psychological treatments in epilepsy, Ramaratnam e t al. (2005) concluded that due to the limited number of studies and methodological concerns there is not enough evidence to endorse psychological treatments in epilepsy. The authors conducted a focused review of randomized controlled trials of psychological treatments in epilepsy. There were three studies that identified anxiety as measured outcome (Sultana, 1987 Helgeson et al, 1990 Olley et al, 2001) . The results of the studies were mixed one study found no change (Helgeson et al, 1990), and the other two studies found significant reductions in symptoms of anxiety (Sultana, 1987 Olley t al, 2001 . The interventions used were psycho-educational programs and relaxation plus behavioral therapy. Depression was the outcome measure in six studies with three studies...

A review of some early studies

Antidepressants Antipsychotics Minor tranquillizers Mood stabilizers Psychostimulants Others (beta blockers etc.) Luchins et al. (1984) used spike activity in perfused guineapig hippocampal slices as an indication of epileptogenicity and reported the effect of a variety of antidepressants. Imipramine, amitriptyline, nortriptyline, desipramine and maprotiline generally increased spike activity, while viloxazine, protriptyline and trimipramine appeared to decrease neuronal excitability. Nomifensine, a drug no longer available, had a biphasic effect, increasing excitability initially, and then producing cessation of spikes. Similarly, doxepin produced a significant increase in excitability, and then significant decreases. In this model mianserin had no effect. Paradoxically, there were some clinical reports of tricyclic antidepressants being anticonvulsant. Ojemann et al. (1983) reported retrospective data, which suggested that doxepin improved seizure frequency in 15 of 19 patients who...

Shared Functional Neuroimaging Abnormalities In Depression And Epilepsy

Hippocampus Tra Mri

Frontal lobe involvement in primary depression has been demonstrated with functional neuroimaging and neuropsychological studies (Baxter et al., 1989). Frontal lobe associated executive dysfunction has been consistently shown in studies on depressive illness. Abnormalities on neuropsychological testing have been correlated to reduced blood flow in the mesial prefrontal cortex (Bench )t al. ) 1993 ) Dolan et al., 1994). Gilliam )t al. performed a pilot study of the association between depressive symptoms, clinical variables, and FDG-PET in 62 consecutive patients with refractory localization-related epilepsy. Age, seizure rate, number of current medications, and scores on the adverse events profile were similar between 55 patients with an abnormal PET compared to the 7 patients with a normal PET. BDI scores were, in contrast, significantly higher in the group of patients with an abnormal PET scan, the majority of which showed abnormalities in the temporal lobes (Gilliam et al., 2004a)....

Common Pathogenic Mechanisms In Depression Anxiety And Epilepsy

In depression and anxiety, changes in the noradrenergic and serotoner-gic systems are implicated as playing a significant role in the expression of these disorders. There appears to be increased noradrenergic activity, contrasting with decreased activity in the serotonergic systems. Pharmacological treatments attempt to modulate this activity. Depending on which medication is introduced, there is a combination of increased or decreased release of the serotonin or NE along with an increase or decrease in receptor activity (Stahl, 1997 ) Ressler and Nemeroff, 2000). It is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce noradrenergic transmission and increase serotonergic transmission (Ressler and Nemeroff, 2000) . If there is a sudden reduction in serotonin there will be an increase in depressive symptoms (Stahl, 1997 ) Ressler and Nemeroff, 2000) . A related hypothesis explaining the effectiveness of SSRIs in treating anxiety indicates that if there is...

The Problem Of Depression Diagnosis In Epilepsy

To conclude, a definite diagnosis of depression in patients with epilepsy can be difficult because a number of symptoms, which are recognized as diagnostic criteria for a depressive episode by the ICD-10 and DSM-IV, may occur in epilepsy secondary to seizure activity or AED treatment (e.g., loss of energy, insomnia or hypersomnia, increase or decrease in appetite, loss of libido, psychomotor agitation or retardation, diminished ability to think or concentrate). Because these symptoms may be present in patients who are not depressed, physicians need to explore fully the mental status of their patients. Inquiring about anhedonia has been suggested as an excellent predictor of the presence of depression (Kanner, 2006) and the use of self-rating instruments can be revealing. However, one of the most frequent methodological errors in research studies on depression and epilepsy is the sole reliance on screening instruments to diagnose depressive disorders. Firstly, a depressive episode can...

Treatment of aggression in epilepsy

Possibly avoid tricyclic antidepressants Care should be taken to establish signs of depression or anxiety, since a close link between these psychopathological states and affective aggression in epilepsy has been established. Both should be treated medically and with psychotherapy at the same time (Goldstein, 1997 Lorenzen, 1973). Behavioural therapy in particular in patients with epilepsy and learning disability has been proven to be very effective (Davis, 1984 Holzapfel, 1998 Rapport, 1983). In the medical treatment of depression in patients with epilepsy, SSRIs or other new antidepressants like venlafaxine should be preferred to the old tricyclic antidepressants (TCA) since the latter are more likely to provoke seizures (Blumer, 1997 Lambert, 1999). In fact, an anticonvulsant effect of SSRIs is well documented in animal models of epilepsy (Browning, 1997 Lu, 1998 Pasini, 1996 Wada, 1995) and is also described in humans (Favale, 1995).

Newer antidepressant drugs

There have been several developments of antidepressants since the tricyclic era. Some drugs have briefly been mentioned above, which were nontricyclic, such as mianserin, maprotiline and viloxazine. However, the major development in the last few years has been of agents that selectively inhibit reuptake and either noradren-aline, or serotonin, or both. The latest generation of antidepressants has been developed to derive their therapeutic benefits from tailor-made action at specific monoamine receptors and reuptake sites, in theory providing better efficacy and better tolerability (Feighner, 1999). Reboxetine is a selective noradrenergic reuptake inhibitor (NARI) with low affinity for histaminergic, cholinergic, dopaminergic and alpha-1 adrenergic receptors. It appears to be equally effective as the tricyclics in treating depression, and there is a suggestion that it may be more effective than fluoxetine (Montgomery, 1997). Venlafaxine is a serotonin-noradrenergic reuptake inhibitor...

Mood improvements by VNS in epilepsy patients

Elger et al. (2000) completed the EO3 study on seizure outcome of VNS, in which their unit participated with some patients in 1993, with a comprehensive psychiatric evaluation. This international multisite outcome study included 14 weeks of a randomized control trial (RCT). Patients were randomly assigned to a low or high stimulation condition (dose-effect study). In order to give patients from both groups the feeling of participating in an optimal treatment condition, patients from the low stimulation group were told that VNS has optimal effects when subjects are just able to recognize the signal. In contrast, patients from the high stimulation group were informed that VNS should be maximized according to subjective tolerability of adverse effects (with 1.75 mA as the predefined maximum). Seizure and psychiatric data were recorded 4 weeks before implantation (baseline) and at the 3- and 6-month follow-ups. Medication was unchanged during the entire duration of the study. From our...

New antidepressant drugs and seizures

Krijzer et al. (1984), used freely moving rats implanted with subcortical electrodes. Almost all of the antidepressants tested caused epileptogenic EEG changes mianserin was the most potent. However, fluvoxamine caused only minimal effects. patients, patients being assessed from 0.2 to 38 months. Interestingly, the mean dose of sertraline in these six was lower than in the other patients. They reported that depressive symptoms resolved in 54 of patients, but also described (Blumer, 1997) the pleomorphic clinical picture of these patients, and the symptom differences from typical major affective disorder.

Role of the interictal and periictal psychopathology in suicide

Kraepelin (1923) precisely described the intermittent dysphoric disorder of patients with epilepsy. Dysphoric episodes present with depressive moods ('very frequently with utter disgust of life and suicidal bent'), irritability, anxiety, headaches, insomnia or at times with euphoric moods. These polysymptomatic dys-phoric episodes occur without external triggers with rapid onset and termination and recur fairly regularly in a uniform manner in the absence of clouding of consciousness. Dysphoric symptoms can be observed as prodromes of an attack or in the aftermath of an attack, but they most commonly appear as phenomena independent of the seizures, with a frequency varying from every few days to every few months. A patient just awakens one day dysphoric, or the dysphoria develops insidiously through the course of a day. As a rule, the dysphoric state lasts from 1 to 2 days but might dissipate after just a few hours. Based on our own observations, we have added anergia and phobic fears...

The interictal dysphoric disorder

Parietal Lobe

Kraepelin (1923) ) and then Bleuler (1949), were the first authors to describe in epilepsy a pleomorphic pattern of symptoms, including affective symptoms with prominent irritability intermixed with euphoric mood, fear, anxiety as well as anergia, pain and insomnia. Gastaut et al. (1955) confirmed Kraepelin s and Bleulers observations, leading Blumer to coin the term interictal dysphoric disorder (IDD) to refer to this type of depressive disorder in epilepsy (Blumer, 2000). Blumers description of the IDD is particularly intriguing. It is characterized by eight key symptoms grouped in three major categories (Table 5.1) labile depressive symptoms (depressive mood, anergia, pain, insomnia), labile affective symptoms (fear, anxiety), and supposedly specific symptoms (paroxysmal irritability, euphoric moods). Blumer preferred the term dysphoria to more accurately translate the original definition of Kraepelin Verstimmungszustand to stress the periodicity of mood changes of the patients and...

Alternative psychosis and forced normalization

In some patients periods of seizure control and normalized EEG appear to be associated with the development of psychoses, which is reversed when seizures recur (the phenomenon as applied to EEG is sometimes known as 'forced normalization'). However, the opposite pattern is also observed, and the true status of forced normalization is rather contentious. The exact mechanism of this pattern is unclear. Antipsychotics, antidepressants and anxiolytic drugs, as appropriate, can be used to treat these episodes. In some individuals the psychosis may be due in part to the introduction of an antiepileptic drug (associated with the remission of seizures), and the replacement of this drug by others is worthwhile. In exceptional cases it is deemed

Cadd And Modeling Anticonvulsant Drugs

Tricyclic Butterfly

FIGURE 3 1.3 Butterfly angles of a tricyclic drug. Many neuroactive drugs have a tricyclic structure. Some are anticonvulsants, while others are antidepressants or antipsychotics. The anticonvulsant tricyclics interact with the voltage gated Na channel protein. The angles formed between the various rings within these molecules define the receptor site with which the molecule interacts these angles can be rigorously determined using quantum mechanics calculations.

Peripheral mechanisms

In mammalians the efferent branch of the vagus plays a decisive role in emotion regulation and expression (Porges 1997 Porges et al., 1994). Furthermore, the vagus is supposed to coordinate and protect the organism's metabolic resources, e.g. by retarding heart rate more or less ('vagal brake') (Porges, 1995). This more theoretical view is confirmed by clinical observations in neuropsychiatric disorders such as depression and anxiety which reveal clear associations between mood and parasympathetic functions (Glassman, 1998 Lehofer et al., 1997, 1999). Diurnal mood variations in some depressed patients may be associated with parasympa-thetic activity (Rechlin et al., 1995). Regarding cardiac measures, it is noteworthy that there is no evidence for altered vagal tone in unmedicated clinical depressions but for increased sympathetic tone (heart rate) which may be due to increased anxiety in depressed patients (Lehofer et al., 1997 Yeragani et al., 1991). Interestingly, experimentally...

Pharmacologic And Psychotherapeutic Treatments For Depression And Anxiety

According to the World Health Organization, by 2020 major depression will be the second leading cause of disability with cardiovascular disease as the leading cause (Michaud et al., 2001). In an editorial, Evans and Charney (2003) stated if an individual has a chronic condition and is depressed there was a poorer prognosis and even increased morbidity and mortality than from the medical diagnosis alone. Additively, co-occurring depression and anxiety is related to poorer prognosis, increased suicide risk, decreased treatment response, and increased functional impairments (Brown et al.) 1996) Sherbourne and Wells., 1997 ) Regier et al.) 1998) Kessler et al.) 1999a) Kessler et al.) 2005a, b) . Generalized anxiety disorder and major depression have been demonstrated to negatively impact quality of life more so than depression alone (Mittal et al.) 2006). Treatment of depression and anxiety will improve quality of life, reduce suicidality, and decrease functional impairments. Leaving...

Treatment oF BIPoLAR DisoRDERs IN PwE

Bipolar disorder is an episodic lifelong disease which may begin with a manic, hypomanic or depressive episode. If the bipolar disorder goes untreated, patients may experience 10 or more episodes in the course of their lifetime. While 4-5 years may elapse between the first two episodes, intervals shorten between subsequent episodes. Bipolar patients constitute about 20 of patients with an affective disorder in non-epilepsy patients the actual prevalence of bipolar disease in PWE remains unknown, however. A population survey carried out in 181 000 households in which 2900 individuals reported a history of epilepsy, found that symptoms of manic depressive illness were identified in 12.2 of PWE, in contrast to 2 of individuals who described themselves as being healthy 33 . The aims of pharmacotherapy in bipolar disorders are to suppress acute major depressive, hypomanic, manic and mixed manic depressive episodes and reinstate and maintain a euthymic state. Just as in co-morbid depression...

Affective disorders and anxiety

Typical constellations of symptoms allowing the diagnosis of a 'major' depressive episode are rare, dysthymic or 'organic' depressive states rather frequent. Blumer and Altshuler (1997) have attempted to introduce a useful classification category of affective disorders in patients with TLE, which they call 'interictal dysphoric disorder'. Predominant features are, among others, depressive mood, paroxysmal irritability leading to outbursts of verbal aggressivity with consecutive feelings of shame, a sudden onset and a brief duration of only days. The enduring remittance of depressive symptoms depends on complete seizure relief (Blumer et al., 1998 Hermann and Wyler, 1989). This finding is supported by our results. Moreover we found that our preoperatively depressed patients showed differences in psychopathology after surgery related to laterality dominant resections led to somatoform symptoms as surrogates of depression (headache, backache, etc.), while nondominant resected...

Anxiety And Depression In The General Population

Based on the National Comorbidity Survey-Replication in the United States, lifetime prevalence rates for depressive disorders is 20.8 with major depression being the most prevalent (16.6 ), and lifetime anxiety disorders identified in 28.8 with specific phobia (12.5 ) and social phobia (12.1 ) as the most commonly occurring anxiety disorders (Kessler et al., 2005a, b). Additionally, the European Study of the Epidemiology of Mental Disorders (ESEMeD) project included representative samples from six European countries (Belgium, France, Germany, Italy, The Netherlands, Spain). This project reported lower prevalence rates of depressive disorders (14.0 ), major depression (12.8 ), anxiety disorders (13.6 ), specific phobia (7.7 ), and social phobia (2.4 ) (Alonso et al., 2004b) . These studies confirm what is considered common knowledge individuals with epilepsy likely have higher prevalence rates of depression and anxiety disorders compared to the general population. separate and distinct...

Druginduced seizures

Almost any psychotropic drug carries a risk of inducing seizures. The risk is highest with the aliphatic pheno-thiazines (e.g. chlorpromazine 1-9 risk , promazine, trifluoperazine). The use of clozapine is associated with a 1-4 risk of seizures and with interictal epileptiform abnormalities. The piperazine phenothiazines (acetophenazine, fluphenazine, perphenazine, prochlorperazine, trifluoper-azine), haloperidol, sulpiride, pimozide, thioridazine and risperidone are thought to have the lowest epileptogenic potential, although firm data are lacking. The risk of seizures with antidepressant drugs ranges between less than 1 and 4 , and varies with the drug category. Agents accompanied by a high risk of seizures include clomipramine and second-generation antidepressants, amoxapine, maproti-line and amfebutamone. The risk of seizures with tricyclic antidepressants (other than clomipramine), citalopram, moclobemide and nefazodone is thought to be lower. The seizure risk with the selective...

Trait or state

It should be noted that 14 is much less than the normally reported 30 of patients with focal epilepsy and depressive mood, and that 51 clearly exceed this number. Comparably, 45 of the seizure-free patients reported good quality of life with QOLIE-10, as compared to only 11 of the patients who continued to have seizures. Although these data are not follow-up data and although depression and quality of life represent only two facets of the whole range of behaviour, these data show quite impressively what a difference the presence or absence of seizures can make. The finding parallels recent findings in children who after successful epilepsy surgery show marked improvement in behaviour disorders (Lendt et al., 2000). Long-term follow-up studies on personality and behaviour disorders are thus badly needed to complete our understanding of the interaction between brain damage, epilepsy and behaviour.

Mechanisms

The mode of action is more or less known for the new substances, if this can be reliably concluded from animal models. In a simplistic scheme, the major antiepileptic mechanisms are either via the sodium channel or GABAergic or antiglutamatergic. It has been pointed out by Trimble that psychiatric problems and in particular depressive disorders are significantly increased with those AEDs which have strong GABAergic properties vigabatrin, tiagabine and topiramate (Trimble, 1997) all three drugs had an increased rate of depressive symptomatology in placebo-controlled trials.

Treatment

In general, all presented studies showed antidepressant drug treatment to be well tolerated, but the reported response rates were highly variable, ranging, for example, with citalopram, between 38 (Khun et al., 2003 and 65 (Hovorka et al.e 2000) at eight weeks. It is evident that the reported variability is influenced by the selection of patients, the lack of a rigorous psychiatric assessment for a correct diagnosis (dysthymia, major depression, bipolar depression, IDD), the presence of other comorbid Axis I disorders, the presence of brain damage, cognitive impairment, a family history for mood disorders and so on. All these variables are taken into consideration very rarely in these studies, but they are essential for a correct interpretation of results. The issue of psychotropic drug treatment of depression in epilepsy is interlinked with that of the proconvulsant or anticonvulsant effects of antide-pressants. Tricyclic antidepressants developed a clinical reputation for convulsant...

Mood Disorders

Depression is the most common comorbid psychiatric condition associated with epilepsy, with a prevalence of up to 50 in patients with recurrent seizures and 10 in patients with controlled seizures.1317 It is generally underrecognized and undertreated and is incompletely understood, but it is thought to be the result of a combination of psychosocial and neurological factors. Although there is an association between chronic illness and depressive disorders, there seems to be an over-representation of depressive symptoms in patients with neurological disorders, and this is further increased if that neurological disorder includes epilepsy.16 Psychosocial factors, including perceived stigma, fear of seizures, discrimination, joblessness, and lack of social support have been implicated in the development of depressive disorders in people who have epilepsy. The relationship between psychosocial factors, depression, and epilepsy show that psychosocial variables are related to epilepsy, not...

Conclusions

Comorbid depressive disorders and suicidal behavior are more likely in patients with epilepsy than in healthy individuals. Likewise, epileptic disorders may be more common in patients with depression. Evidence exists for a close, potentially bi-directional relationship between the two disease states, with common underlying anatomic, pathologic, and functional abnormalities. Unresolved issues include establishing a direct causal link between depression and epilepsy, determining optimal treatment strategies for patients with depressive disorders in the setting of epilepsy, and whether the pathophysiologic characteristics of this subgroup of patients and their response to treatment may substantially differ from patients with primary depression. Preliminary data with standard antidepres-sant regimens, and psychiatric referral when appropriate, appear to be effective initial interventions. It is unknown at this time whether early treatment of a depressive

Noradrenergic system

Naritoku et al. (1995) investigated regional c-Fos immunoreactivity and reported activation of the locus coeruleus (LC) by therapeutic VNS. By means of lesion studies in animal models of epilepsy, Krahl and coworkers have demonstrated that the antiseizure effect of injected norepinephrine depends on the vagus (Krahl et al., 2000) and that the seizure-attenuating effect of VNS is mediated by and totally depends on LC activity (Krahl et al., 1998). The locus coeruleus is the major origin of the noradrenergic system in the brain and has projections to brain regions which are involved in both mood regulation and epileptogenesis (e.g. thalamus, hippocampus, amygdala and isocortex). Norepinephrine has an inhibitory influence on postsynaptic neurons which may explain the antiseizure effect of activating the LC by VNS. At the same time, the noradrenergic system is involved in neuropsychiat-ric disorders like depression one major effect of tricyclic antidepressant medication is to increment...

Cortical inhibition

From clinical experience with ECT, a third hypothesis may be derived inhibition of cortical activity, as the major mechanism of ECT (Sackheim et al., 1996), may enhance depressive mood states and may improve seizure control. Since VNS seems to produce rather similar effects as ECT, one may speculate also that VNS increases the inhibitory influences on cortical tone. However, evidence confirming this speculation and replication of the findings from ECT is missing (Hammond et al., 1992 ).

Efficacy

Table 15.2 summarizes the drugs of the SSRI and SNRI families that have been found to be effective in the treatment of primary depressive disorders, and the recommended starting and maximal doses. From the stand-point of efficacy, the choice of SSRI or SNRI must depend on whether the patient has only a depressive episode or a mixed depression anxiety (and or panic) disorder. Furthermore, the elimination of co-morbid anxiety symptoms with a depressive disorder is as important as that of symptoms of depression, as the former have been associated with an increased suicidal risk 30 . There are also data suggesting that SNRIs may be more effective in patients with physical symptoms (pains and aches), fatigue and psychomotor slowing, which can be relatively common complaints in depressed patients. Since a successful treatment of any depressive disorder is one that yields complete symptom remission, eradication of these physical symptoms should be always considered, as residual symptoms are...

Adhd In Adults

Presenting symptoms and history may need to be corroborated with third parties. Psychiatric disorders most commonly associated with ADHD in adults are anxiety, substance abuse, bipolar disorder or major depressive disorder. Lower educational and occupational achievement has been reported.

Conclusion

Suicide in epilepsy results from the psychiatric disorder of temporal lobe epilepsy that is, from a severe dysphoric disorder, from interictal psychosis (associated with preceding and concomitant dysphoric disorder, and at times with command hallucinations), or from a severe postictal depressive state. These psychiatric disorders develop gradually as seizure-suppressing mechanisms become established or, at times, upon acute engagement of the inhibition. Suicide in epilepsy has increased with our improved ability to suppress seizures. Suicide in epilepsy tends to occur precipitately during a 'fit of melancholy' (as van Gogh described the depressive mood of his dysphoric episodes) and is often not anticipated. However, there are usually warnings that precede a suicide. Upon the occurrence of episodes of suicidal moods, prompt intervention is required with psychotropic medication, chiefly of the antidepressant type, and with careful follow-up that includes adjusting the psychotropic...

Antipsychotic drugs

As with the newer antidepressants, there is much less information about the effect of the atypical neuroleptics on the seizure threshold, with the single exception of clozapine. The latter was known to be proconvulsant from early studies, the seizures being a dose-related effect. The incidence of seizures rises to about 5 at doses of 600 mg, although EEG changes may be recorded at lower doses. The seizures are often myoclonic, but can be generalized tonic-clonic, or partial, depending on the individual patient.

Electrophysiology

Patients with panic attacks have been reported to have an increased amount of paroxysmal EEG activity (Hughes, 1996), with this occurring up to four times more often than is the case in patients with a depressive illness. Temporal lobe abnormalities have been highlighted in brain electrical activity mapping (BEAM) studies in patients with panic attacks.

Case reports

This manic state, lasting for 4 weeks, gradually turned into a depressive one. Two months after the operation, he felt quite upset and lost interest in all activities. He became so agitated that he could not stand still for a moment, and walked around restlessly. He complained of slowed thinking and difficulties in making decisions. After treatment with tricyclic antidepressants, his mood improved steadily, but only gradually, over half a year. Six months after the operation, he set out to do his previous work and his relations with colleagues improved dramatically. A year after the operation, his mood was stabilized without the help of antidepressants and he was accepted once again as the manager of the kimono shop. He has been completely seizure-free for 4 years postoperatively. Moreover, neither the previous dysphoric episodes nor the mood disorders have recurred.

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