by Dr. Alan Lowe, Neuropsychiatry-Epilepsy Program Toronto Hospital, Western Division
What is depression?

Major Depression (MD) is a psychiatric/medical syndrome defined by the Diagnostic and Statistical Manual-4 (DSM-IV) with symptoms as listed in Table I.1 DSM-IV requires that symptoms last longer than two weeks and persist nearly every day. Major depression differs from normal sadness in that the symptoms are more frequent, persistent and severe. The symptom of depressed mood, for instance, would occur nearly every day for at least two weeks in Major Depression whereas in normal sadness depressed mood may last only a day or two. The symptoms of Major Depression are more disabling and can result in deterioration and impaired functioning in almost all aspects of a person’s life, such as one’s ability to perform one’s job, socialize, and care for one’s self and family. Decreased functioning is usually the result of depressed mood, low energy and lack of motivation.

  • Depressed Mood
  • Weight Gain/Loss
  • Insomnia/ Hypersomnia
  • Restlessness/ Lethargy
  • Worthlessness/ Guilt Feelings
  • Decreased Interest/ Pleasure
  • Concentration/ Decision Making Difficulties
  • Recurrent thoughts of Death/ Suicidal thoughts

It is estimated that Major Depression effects between 10-20% of the general population. It is found that women suffer from MD more than men in the ratio of 2:1.2 Fifty percent suffer MD before the age of 40 years and the other half afterwards. Risk factors for depression include a family history of depression, alcoholism and parental loss at an early age.2

What causes depression?

Many factors can contribute to MD and no one factor is entirely responsible for it. Factors are complex, inter-related and overlap. In any given individual suffering from depression it is felt that usually a combination of factors play a role in causing the depression, with certain factors contributing more than others. These factors are usually separated into biological and psychological categories to help understand them better and facilitate treatment.

Biological causes of depression include such factors as changes in brain chemistry, hormonal effects, kindling (i.e. repeated sub-threshold stimulation), genetics, medical/neurological disorders and medication.2 It is felt, for instance, that people suffering from depression may have low levels of brain norepinephrine, serotonin or dopamine and medical treatment is aimed at trying to get these chemicals back into balance by antidepressant treatment. It is also felt that certain medical/neurological conditions such as infection and cancer can predispose one to depression, as can certain medications. Genetics certainly play a role and children of depressed parents are at a 10-15% risk for depression themselves.2 Twin studies show high concordance rates of up to 50% for monozygotic twins and 25% for dizygotic twins implicating genetic causes for depression.2

there are many psychosocial factors that can contribute to depression. Environmental stress and significant life events, such as the loss of a parent at an early age, loss of a spouse and family distress can contribute to depression.2 there are many psychological models and theories about how depression develops. The psychoanalytical model emphasizes the role of internal conflict, feelings of loss, significance of meaning and emotional states in contributing to depression. Behavioural models emphasize poor coping styles/techniques and learned helplessness to control external events.2 Cognitive theories emphasize negative perceptions/views about oneself, one’s life experiences and one’s future.2 Both biological and psychological factors are felt to contribute to depression, with much overlap between them.

What is the course of depression?
The course of Major Depression is generally good. Eighty percent of people suffering from depression recover with treatment, while 20% continue on a chronic course.2 If there is a chronic and recurrent course the average number of lifetime episodes is around five, with decreased times between each and increased severity with each episode.
What are the consequences of depression?

If Major Depression is left untreated the average length of an episode is about 10 months, but this may lead to the development of other problems, such as alcoholism or suicide.2

Although Major Depression is generally treatable with good outcome, it often goes unrecognized and unnecessarily adds to human suffering, wasted potential and economic loss. Deterioration and impaired functioning in all aspects of one’s life are serious consequences of depression.

the gravest consequence of depression is that about 15% of those suffering from it commit suicide.2 Some of the risk factors for suicide are severe refractory depression, extreme feelings of hopelessness, the presence of psychotic symptoms such as delusions and hallucinations, personality disturbances, alcohol or substance abuse, social isolation, unemployment and an unresponsive family.2 Males generally commit suicide more than females and females attempt suicide more than males.2

Good outcome and resolution of depression is associated with mild episodes, few hospitalizations, the presence of good friendships in adolescents, stable family functioning, good social functioning for more than five years and the absence of alcohol or drug abuse, psychotic symptoms or other psychiatric disorders.2

What is the treatment for depression?

The type of treatment for depression usually depends on its severity and should be tailored to suit the individual. Mild depression may require psychological therapy only. This may take the form of psychotherapy, supportive therapy, cognitive therapy, interpersonal therapy, group therapy or family therapy. The aims of each are different and the therapist involved in one’s care best determines which type of therapy is suitable for the individual. Psychotherapy, for example, focuses on talking about one’s emotions, conflicts and motivation.2 Cognitive therapy focuses on correcting negative perceptions/views.2 Behaviour therapy focuses on developing better coping behaviours and Interpersonal therapy would focus on interpersonal issues.2

Moderate to severe depression usually requires a combination of psychological and medication treatment. Antidepressant medication is usually used to treat depression, but other medication or treatment may be required if there are other severely disabling symptoms present.

What are the medications for depression?

there are many types of antidepressant medications. The newest antidepressants include the Serotonin Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) and Reversible Monoamine Oxidase Inhibitors (RIMAs). They are commonly prescribed presently for Major Depression because they are safe and have fewer side effects than the older antidepressants, which include the Tricyclic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs). Table II lists various types of commonly prescribed antidepressants.

Common side effects of the newer antidepressants include stomach upset, drowsiness or headache, but most of the time they are well tolerated and help people feel and function better.

Table II – Names of Antidepressants


Type Generic Name Trade Name
SNRI Venlafaxine Effexor
SSRI Fluoxetine Prozac
SSRI Sertraline Zoloft
SSRI Paroxetine Paxil
SSRI Fluvoxamine Luvox
SARI Nefazodone Serzone
SARI Trazodone Dexyrel
RIMA Moclobemide Mannerix
MAOI Phenelzine Nardil
MAOI Tranylcypromine Parnate
MAOI Isocarboxazid Marplan
TCA Clomipramine Anafranil
TCA Impipramine Tofranil
TCA Amitriptyline Elavil
TCA Nortriptyline Pamelor
TCA Protriptyline Vivactil
TCA Desipramine Norpramin
TCA Trimipramine Surmontil
TCA Doxepine Sinequan
TCA Maprotiline Ludiomil
TCA Amoxapine Ascendin
What is the risk for people with epilepsy?

People with epilepsy are felt to be at greater risk for Major Depression (MD) than the general population and those suffering from other medical conditions. It is felt that up to about one third of those with epilepsy suffer from associated depression.3,4,5,6 Many factors, as previously mentioned, can contribute to MD in an individual with epilepsy. No one factor is entirely responsible and it is felt that it is usually their combined effect that generally contributes to depression, with one factor perhaps predominating more than another in a given individual.

Seizure activity, poor seizure control and kindling like phenomena may be causes of depression.7 Some people may also experience Postictal-Depression which is depression after seizures.7 there is a suggestion that those suffering from left temporal lobe epilepsy (L-TLE) are more predisposed towards depression, as well as those who have underlying brain disturbances producing seizures.3,8,9 Psychosocial factors predisposing to depression in people with epilepsy include adjustment difficulties, the limitations and restrictions which the disorder imposes, as well as the unpredictable nature of the seizures and the associated feelings of helplessness and loss of control over one’s life.10

Rarely, depression may be a side effect of anticonvulsant medication or from combinations. Phenobarbital has a 5% risk of causing depression, followed by Vigabatrin, Lamotrigine and Phenytoin, possibly due to folate deficiency.10,11,12,13 However, not all anticonvulsants are associated with adverse effects on mood, as Carbamazepine and Valproic Acid can in themselves help stabilize and improve mood, and are frequently used in psychiatry to treat manic depression and depression.10,14,15

What impact can depression have on people with epilepsy?

Depression can have a significant negative impact on people with epilepsy. Depression can result in decreased functioning in all areas of a person’s life, lead to decreased compliance with medication and increase the risk of seizures.3,10

Increased emotional stress and depression can result in worsened seizure control and increased seizure frequency. 3,16,17,18,19 Table III illustrates varying seizure frequency with different emotional states.17 the most serious consequence of depression associated with epilepsy is suicide. The risk of suicide is five times greater than the general population for people suffering from both depression and epilepsy and 25 times greater if the person suffers from temporal lobe epilepsy.3,10,20,21 Reasons why people with epilepsy are more at risk for suicide may be due to the underlying brain disturbances causing the seizures and depression, the psychological impact of helplessness and hopelessness from uncontrolled and unpredictable seizures, and the ready availability of potentially lethal anticonvulsant medication if taken in overdose or in combination with drugs and alcohol.3,10,20,21

How is depression treated in people with epilepsy?

Treatment of depression in people with epilepsy can improve mood, energy and functioning. It can also help reduce seizure risk, seizure frequency and the risk of suicide.

the approach to the treatment of depression in epilepsy is generally the same as that for those without epilepsy. A combination of antidepressant medication and psychological therapy is best. The specific type of treatment a given individual receives will vary, as treatment must be tailored to suit each individual person. What’s good for one person may not be good for another. So comparing treatment between oneself and another should be avoided. Specific questions regarding one’s therapy and reasons for it should be directed at one’s own therapist/doctor, as well as discussion about suitable alternatives.

Although the approach to the medical treatment of depression in people with epilepsy is very similar to the treatment in non-epileptic people, particular attention is paid to the optimization of seizure control. As in the management of epilepsy, attention to seizure control, monitoring potential drug interactions and antiepileptic drug (AED) levels still applies. Decreasing risk factors for depression include optimization of seizure control, (perhaps) medication adjustment, consideration of alternatives and minimizing polypharmacy. with the development of the newer antidepressants, people suffering from epilepsy can feel more secure about the safe and effective treatment of depression medically.

Taking extra medication is of great concern for those with epilepsy. There is also concern about drug interactions and their effects on seizure control. Antidepressant therapy is usually temporary and not lifelong, unlike anticonvulsant therapy. Depending on the severity of the depression one usually only needs to be on the medication for six months to one year.2 If the depression is significantly refractory/disabling, sometimes, but rarely, the person may need to stay on them most of their life.2 Generally the benefits outweigh the risks of temporarily taking antidepressant medication along with anticonvulsant medication, as they help alleviate depression, decrease suicidal risk and can help seizure control.

Do anti-depressants affect seizure control?

The newer antidepressants were designed not to be toxic/lethal in overdose as compared to the older TCA antidepressants. They are significantly safer and have fewer side effects. The newer antidepressants are generally associated with no change in seizure frequency and may even decrease seizure frequency in some people with epilepsy.22,23,24,25,26,27,28,29 they may help seizure control by alleviating emotional distress and depression (which are triggers for seizures), by improving compliance, AED levels and functioning. Generally the newer SSRI antidepressants should be considered first choice in the medical treatment of depression in epilepsy.

There was much concern and caution regarding the use of older TCA antidepressant medication as these could lower seizure tdreshold and be associated with seizures at toxic/higher doses.10,30,31,32,33,34,35,36 Although they do have a higher risk of causing seizures most observations have found this not to be clinically significant.10,30,31,32,33,34,35,36 However, because of the risk of provoking seizures with the older TCAs and some of the newer agents such as Amoxapine, Maprotiline and Bupropion, these particular agents should generally be avoided in people with epilepsy.37,38,39,40 the least likely to provoke seizures being the SSRIs and the most likely to provoke seizures being the TCAs and Bupropion.

Caution and experience on the part of the doctor using the newer antidepressant medication still applies, but the rationale not to use them for fear of worsening seizures is no longer valid. Avoiding use of these potentially very helpful medications when needed may result in added morbidity and mortality in those suffering from depression and epilepsy. Another form of medical therapy for severe depression is electroconvulsive therapy (ECT). ECT is the induction of a controlled seizure to treat depression. It can also be used to help people suffering from depression and epilepsy and clinical observation finds that it does not worsen seizure control.41

In terms of their interaction with AED, antidepressants can be associated with slight increases in AED levels. The effect usually is not clinically significant and in some cases may account for better seizure control.42,43,44 However, levels should be monitored and particular caution should be undertaken when many AEDs are involved to guard against potential toxicity.42,43,44

Can psychological treatments help depression?

Many psychological treatments can be helpful for depression in epilepsy especially when combined with medical treatment. Such treatments include psychotherapy, cognitive behaviour therapy to develop new coping skills, relaxation therapy and supportive counselling. The type of treatment will depend on the individual’s condition, which one the therapist/doctor feels is best for the patient, and what the patient feels most comfortable with. Generally, all are potentially helpful.

What should you do if you suffer from depression?

If you feel you are suffering from depression you should seek appropriate help from your family doctor or neurologist. They may in turn refer you to a psychiatrist, neuropsychiatrist or psychologist who is experienced in treating depression. Talking and seeking support from family, friends and other health care workers such as nurses, social workers, or occupational therapists/counsellors is also helpful. If your depression is severe and you are in crisis you should contact your doctor and go to your nearest hospital emergency room.

Avoiding isolation, complying with medical treatment and educating yourself and your family about depression will help you regain control of your situation.

Families can help people who are depressed by providing support/understanding, avoiding blame, decreasing conflict, fostering a sense of autonomy and independence, and taking part in learning about depression. They can be significantly helpful in encouraging the person to seek help when necessary.

In Conclusion

People with epilepsy are at risk for depression and its serious consequences. However, treatment is available and it is safe and effective. People with epilepsy should be able to feel good and function optimally.


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