Still on antidepressants

There have interesting feedbacks on the last piece on Amitriptylline. One said she now understood the hot flushes she experienced after being put on Amitriptylline. Sweating forms part of the body’s mechanism to regulate the body’s temperature. By sweating the internal systems ‘cool down’.

So when you are on a medication such as Amitriptylline that dries up secretion then heat may accumulate within you and manifest as hot flushes. Someone said he was living in a flat with two other persons who are both on therapy for depression.

One is on Amitriptylline and the other was on Fluoxetine. He wanted to know why. Amitriptylline belongs to the class of antidepressants referred to as Tricyclic Antideressants (TCAs).

These have three rings of atoms. Other examples are Imipramine Doxepin. Fluoxetine belongs to another class of antidepressants known as Selective Serotonin Reuptake Inhibitors (SSRIs).

Basically the brain communicates with itself through the use of special chemicals known as neurotransmitters such as serotonin, norepinephrine and dopamine.

There is a correlation between the amounts of these chemicals in the brain and a person’s mood. While low levels of serotonin and norepinephrine have not been proven to cause depression it is widely believed that an increase in these chemicals in the brain is associated with improved people mood in depressed people.

This is basically what TCAs and SSRIs seek to do in depressed but through different mechanisms of action.

TCAs increase the levels of serotonin and norepinephrine in the brain by slowing their re-uptake (or re-absorption) at nerve cells.

TCAs also block histaminic, cholinergic and alpha1-adrenergic receptor sites. This lack of selectivity is what accounts for such untoward effects such as weight gain, dry mouth, constipation, drowsiness and dizziness.

SSRIs on other hand are highly selective by strongly blocking the re-uptake of serotonin and to far less extent (as compared to TCAs) prevent the re uptake of norepinephrine. SSRIs therefore have fewer side effects than TCAs.

Again while TCAs can easily be defined by their structures SSRIs have very varied structures, e.g. Fluoxetine, Fluvoxamine, Paroxetine, Sertraline.

I must say that both TCAs and SSRIs are effective for the treatment of depression. TCAs have been found especially effective for depressed in-patients (Anderson et al. SSRIs vrs TCAs. Meta-analysis of effects and tolerability, J.Affect disorder. 2000, 58(1).

This effect has been attributed to TCA inhibition of both serotonin and norepinephrine. TCAs are known to be more effective for severe depression.

They are used as first-line treatment for patients with severe (melancholic/endogenous) depression (Boyce et al. The place of TCAs in the treatment of depression. Aust, N.Z. J. Psychiatry 1999).

The remission rate for TCA is 44.1 per cent compared to 37.7 per cent for SSRIs (Machado et al. Remission, drop-out and adverse drug reaction rates of major depressive disorder.

Meta–?analysis of head-to-head trials. Curr.med.res.opinion 2006). SSRIs have better side effect profile than TCAs for both acute and long term treatment even though.

SSRIs are generally known to cause more sexual dysfunction than TCAs. SSRIs also cause more headaches, agitation, insomnia and tremor than TCAs. SSRIs have more gastrointestinal side effects than TCAs.

SSRIs have less interactions with alcohol, antihypertensives and sedatives. There is less dropout for persons on SSRIs than those on TCAs.

The untoward effects of TCAs could also limit up titrating doses even when these is a compelling need. SSRIs have a wide therapeutic index, that is, a wide gap between the dose that is effective and the dose that could be potentially toxic.

This contracts with TCAs where just taking just 5x the therapeutic dose could be potentially fatal.

In reality the goal behind the rational development of the SSRIs was to either maintain or enhance antidepressant efficacy, increase the therapeutic index (that is the safety margin between the effective and toxic dose), improve the tolerability profile, and reduce the risk of relevant drug interactions. As a result, in current practice SSRIs seem to have replaced TCAs as first choice in the treatment of depression.

It is very likely in many cases for one to receive trial of SSRIs as first line in the treatment of depression at an optimal dose. The health care provider need not bother about safety and dose as seen in the the use of TCAs.

Onset of action of antidepressants is delayed and as result clients put on therapy can be very unpredictable (initially) and need to be closely monitored. I have earlier mentioned the interaction between TCAs and alcohol.

I do not expect persons on antidepressants to be taking alcohol. TCAs have antihistaminic effect. Antihistamines as a class of medications are typically used to treat allergies. A typical example is Chlorpheniramine (Piriton).

Its major side effect is sedation. We therefore advise clients on such medications not to take the antihistamine together with alcohol.

Therefore if TCAs have antihistamines effect then there is risk of potentially serious depression of the central nervous system. One does not need to bother about this effect when using SSRIs because they have been designed to avoid blocking the histamine receptor.

Blockade of the alpha 1–?adrenergic receptor leads to a fall in peripheral resistance and consequent fall in blood pressure. This is the reason behind the use of antihypertensives such as Terazosin, Doxazosin in some situations. TCAs also block alpha1 adrenergic receptors.

Therefore using them together with such antihypertensives could lead to more pronounced fall in blood pressure and cause falls and traumas.

SSRIs have been developed to avoid this particular effect on alpha1-adrenergic receptors. On the face value the acquisition cost of SSRIs may be higher than TCAs but the health care provider will usually consider other factors as well.

For example the cost of administering the treatment e.g. the number of physician visits, ancillary tests needed to monitor treatment.

The cost of treating potential adverse effects that range from mild to that resulting from overdose of a TCA. The cost of adverse outcome due to adverse drug interaction.

The cost of effective treatment balanced against the cost of not effectively treating the disease condition e.g. loss of productivity, increased relapse rates from patients discontinuing treatment (dropouts) due to side effects of the drug. SSRIs unlike TCAs are easy to administer.

Many health care providers start low when using TCAs for the first time in a client because of side effects. As always, your health care provider is the best resource to address any issues you may have with your medication.

There is another class of antidepressants known as the Monoamine-oxidase inhibitors (MAOIs). MAOIs have dangerous interactions with some foods and drugs and should be reserved for use by specialists (BNF 68).

 By Edward O. Amporful

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