Until the 1950s there were no effective drugs available for depression. The world’s first truly effective antidepressant is imipramine, and after more than half a century, it is still in use today. And though we now have a plethora of antidepressant drugs none are more effective than imipramine. Although Imipramine is a wonderful antidepressant, it has some unpleasant side effects such as dry mouth, constipation, and blurred vision. It is toxic in overdose and can lead to abnormalities of rhythm in the heart and even cardiac arrest (perhaps not the ideal drug to leave in the hands of a depressed and suicidal patient). 

In the 1970’s scientists working at the American drug company Eli Lilly discovered fluoxetine, a new class of antidepressants called SSRIs (serotonin specific reuptake inhibitors). It was easy to take (one capsule a day), did not have the unpleasant side effects of imipramine and was much less toxic in overdose and could therefore be safely given to patients who were suicidal. It was to become one of the most successful drugs in history and at its peak reached sales of three billion dollars. Marketed under the name Prozac it achieved cult status inspiring books -“Listening to Prozac” and “Prozac Nation” and even a film.
The prescription of antidepressants especially in the US and other Western countries has continued to rise and in the US now is only second to heart medication. In 2008 an article in the Scientific American titled “The Medicated Americans” noted that nearly 10 percent of Americans were on antidepressant prescriptions. Does it mean that the incidence of depression has increased over time? The answer is both ‘yes’ and ‘no’.

The respected psychologist Martin Seligman summarised the results of a large scale study done in the US, “If you’re born around World War II, the lifetime prevalence of depression seemed to be about 5 percent. If you were born starting in the 1960s, the lifetime prevalence seemed to be between 10 and 15 percent, and this is with lives incomplete.” Seligman also noted that the age of onset of the first depressive episode has dropped. A generation or two ago the onset of depression occurred on average at age 34 or 35 but recent studies show the mean age for the first bout of depression to be 14 years old. So there is evidence that the prevalence of depression has increased but not as much the number of prescriptions for depression. 

Most of these prescriptions were not written by psychiatrists but by general practitioners. Therefore it is reasonable to assume that most of these prescriptions were not given for clinical depression. Doctors (at least in the States) have been quick to prescribe antidepressants for any complaint of being moody, sad or being down without actually checking carefully whether the patients have the definite features of the disease condition called depression. They have used these medicines as a “happy pill” rather than as antidepressants.

As I mentioned before, a clinical depression has very distinctive features which should be there almost every day and should have lasted for more than two weeks. Transient unhappiness due to life circumstances does not respond to antidepressant medication. Currently there are more than 30 different kinds of antidepressant medicines, each with different side effects. These are less severe than the old tricyclic antidepressants like imipramine. 

An important fact that people starting on antidepressants should remember is that unlike most medicines, antidepressants do not have an immediate effect. There is a delay of three weeks or longer before the patient feels a difference. Scientists are not sure of the reason for this delayed effect. It is postulated that changes in the nerve transmission of areas in the brain that play a role in emotion take place slowly. Unfortunately the side effects of the antidepressant drugs occur almost immediately. Even the newer antidepressant drugs do have side effects. For example fluoxetine (Prozac) may cause irritation of the stomach, with flatulence and nausea. The person may also become a bit more anxious and jumpy due to the stimulant effect on the nervous system. Fortunately these side effects become less with continued use as the body adapts to the medicine. Due to this effect a depressed patient starting on antidepressant medication may feel worse than before during the first three weeks of treatment.

Antidepressant drugs have had a bad press in recent years. One concern has been that some types of antidepressant drugs increase ideas of suicide especially in younger people. In response to these concerns the US Food and Drug Administration has issued a black box warning for antidepressants and suicidal thoughts and behaviour in children and young adults. Is this concern justified? A recent study which analysed all the data from studies in younger patients on two popular antidepressants, fluoxetine and venlafaxine found no increase in suicidal thoughts or behaviour. Almost all reports of increase in suicidal thoughts or acts while on antidepressants have been from Western countries and tied in with litigation. In contrast studies on the effects of antidepressants have demonstrated over and over that if used in proper dosage for correctly diagnosed depression it significantly reduces the risk of suicide. 

It is important for persons who think they may have a depressive disorder to confirm their diagnosis by seeing a mental health specialist before starting on antidepressants. It is also important that once started medication is continued until there is improvement.

Are there any other treatment options other than medication? One option is electroconvulsive therapy or ECT. In 1937 an Italian neurologist named Ugo Cerletti thought that people who had epilepsy were less likely to have schizophrenia and therefore if a fit could be artificially induced in persons with schizophrenia they would improve. Having first tested his electroshock machine on dogs he was ready to test it on humans. It is said that his first patient was a vagrant picked up from the central railway station in Rome who was believed to have schizophrenia. After being given several shock treatments, the patient made a remarkable recovery. 

Initially ECT was mainly given for patients with schizophrenia. Though some of them did recover well it was later realized that ECT was more effective for patients with depression. Even people with severe depression had quick and dramatic recoveries with ECT.

‘One Flew Over the Cuckoo’s Nest”, the Oscar winning American film starring Jack Nicholson portrayed ECT in a negative light where it was used for control and punishment rather than for treatment. In the olden days the fit was unmodified and a large number of patients suffered fractures of the spine due to the violent seizures. This is a far cry from modern day ECT where the patient is given a short acting general anaesthetic and succinyl choline, a drug that paralyses the muscles. After the patient is put to sleep, two electrodes are placed on the patient’s head and an electrical impulse lasting only a few seconds is set off. The patient is woken soon after from the anaesthesia and usually suffers nothing worse than a headache and a short period of amnesia. In an otherwise fit person ECT can be safely given as an outpatient procedure. Does ECT cause brain damage? Repeated testing of persons, some who have had several hundred shock treatments in their lives, has shown no permanent damage to the brain. 

As previously mentioned all antidepressant drugs available today have a lag period of more than three weeks before they show an effect. ECT is the only antidepressant treatment available today that works faster than antidepressant drugs. In a person who has stopped eating and drinking, is in severe depression, or in an elderly person where the side effects of antidepressants can be dangerous, ECT is a lifesaving procedure. The factors that prevent the more widespread use of ECT in the treatment of depression are public prejudice and the timidity of some clinicians. The respected Oxford Textbook of Psychiatry states- “The safety of modern ECT is such that even the frailest and systemically ill elderly can be safely treated with ECT. We acknowledge no known absolute contraindication to ECT other than the lack of skill of the clinician”.
Sometime ago one of the doctors working in my unit asked a number of patients who had undergone ECT about their experience. The majority were highly positive and said though initially they were nervous, having undergone the therapy they would not be afraid of going through treatment again and would recommend the treatment to anybody who needs it. Prof. Max Fink in his book “Electroshock –Restoring the Mind” quotes a practising psychiatrist who had ECT for depression, “After the first treatment, I felt a blunting of the acute sadness of the depression. Whereas before treatment I became tearful with very little provocation and felt intensely sad out of all proportion to the stimulus, after one single treatment I was no longer crushed by any chance sadness. The troublesome symptom of irritability also subsided early in the course of treatment”. The psychiatrist added, “I hope that this account will help to dispel the erroneous belief that ECT is a terrifying form of treatment crippling in its effects on the memory and in other ways. The technique is today so refined that the patient suffers a minimum of discomfort, and the therapeutic benefits are so great in those cases where it is indicated that it is a great pity to withhold it from mistaken ideas of kindness to the patient”.

A word of caution here: ECT though an excellent treatment where it is indicated, is not a panacea for all psychiatric illnesses. It has been shown to be extremely effective for severe depression, some types of schizophrenia, bipolar illness and some medical conditions such as catatonia and Parkinson’s disease. It is not effective, and should not be used for, anxiety related neurotic type of disorders such as obsessive compulsive disorder, mild depressions brought on by life problems and acute attacks of anxiety (panic attacks). 

A reader’s query

A reader’s query: Mrs. M.G. from Mount Lavinia

My 44- year-old spinster daughter has the following behaviours whenever she gets her menstrual periods. She becomes irritable and moody and fights with her parents. She loses her appetite for food and at times cries loudly. After 4 or 5 days she becomes normal again. This pattern has recurred for several years. She refuses to see a doctor. 

Your daughter has a type of depression now known as Premenstrual Dysphoric Disorder. This is not a new entity and has been previously called by names such as premenstrual syndrome but it is only now that it has been given a place as a separate type of depression. In this condition the person becomes moody, irritable and anxious prior to menstruation. These symptoms resolve once menses start or shortly thereafter.

To diagnose this condition, these changes should occur in most cycles for at least a year and should affect work and functioning significantly. It responds to antidepressants given in lower than the usual dose. Treatment should be started prior to the predicted onset of symptoms. There are other treatment options as well. Please do encourage your daughter to see a doctor and get treatment as she is suffering unnecessarily.

Next month: The treatment of depression with psychotherapy

MediScene continues our series on mental illness by Consultant Psychiatrist Prof. Raveen Hanwella. Prof. Hanwella who is attached to the National Hospital is Head, Department of Psychological Medicine, Faculty of Medicine, University of Colombo.

Something bothering you? Please write in to Prof. Hanwella C/o MediScene, The Sunday Times, No. 8, Hunupitiya Cross Road, Colombo 2 or e-mail: raveensundaytimes@gmail.com