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There is evidence for tricyclic-antidepressants' efficacy in the treatment of various anxiety disorders, especially when they don't respond to other drugs but as with all medication, their side effects are many.

Tricyclic antidepressants were introduced in the 1960's and originally prescribed for depression but their use became more widespread and they were increasingly used to treat anxiety conditions such as obsessive compulsive disorder (OCD). The term “tricyclic” refers to the three rings, or atoms, in the drug's chemical structure and they work by inhibiting the reabsorption of both serotonin and norepinephrine.

There is a considerable evidence base for the “classical” tricyclic-antidepressants' efficacy in the treatment of panic disorder and OCD especially, but there is also support for their use in other anxiety disorders as well, apart from social phobia. The disadvantage of this group of drugs, and one of the reasons they fell out of favor, is their considerable side effects and toxicity in overdose. Apart from established side effects, recent research has shown that they were linked in a study of 15,000 people to an increased risk of cardiovascular disease (CVD); the study showed that tricyclics were linked to a 35 percent increased risk. Therefore prescribing this type of anti-depressant is usually seen as a last resort when other treatments have proved unsuccessful. 

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants are used in the treatment of panic disorder, PTSD, generalized anxiety and depression that occurs with anxiety when SSRIs (specific serotonin reuptake inhibitors) don't work or leave residual symptoms. Of this group of medications, imipramine has been the focus of most research and found to be especially effective at reducing panic attacks and improving low mood and they are believed to be non-addictive or unlikely to be tolerance-developing.

However, they tend to take a long time to work – anything from four to twelve 12 — and have anticholinergic effects; that is dry mouth and associated dental issues, visual disturbance, hyperpyrexia, and on occasion, dementia-like symptoms. They can also cause postural hypotension (feeling faint or dizzy when standing up) and induce insomnia, tremors and also weight gain. They are not recommended for patients with glaucoma or certain heart abnormalities or those with prostate issues. Unlike SSRIs, they cannot be taken when pregnant or breastfeeding.

Anticholinergic side effects can include: dry mouth, blurred vision, constipation, difficulty urinating; postural hypotension (dizziness on standing up); tachycardia (rapid heart beat), loss of libido (sex drive); erectile dysfunction; increased sun sensitivity; weight gain; sedation (sleepiness); increased perspiration. These side effects will often subside over time, but some people do experience side effects like feeling jittery, irritated, more or less energetic, and insomnia, even on very low doses.

Imipramine (Tofranil and others)

Imipramine is thought to be beneficial in panic disorder, generalized anxiety disorder, and post traumatic stress disorder. Research indicates that it blocks panic attacks in 70 percent of people. However, it has not been found to be very useful for anticipatory anxiety and response to the medication can be very slow. Unfortunately its effects do not appear to be long-lasting as one quarter to one half of those prescribed relapse after ceasing the medication.

Alongside the side effects listed for tricyclic-antidepressants generally, it can initially increase anxiety, although this usually diminishes over time. Unfortunately its anticholinergic effects are more severe than with most other antidepressants and some people (approximately 20 to 25 percent) report a feeling of “jitteriness” when taking it initially. Weight gain is a possibility and males often report reduced libido; additional side effects include palpitations, sweatiness and sedation. As many as one third of patients find the side effects so intolerable that they are unable to continue taking them.

Desipramine (Norpramin, Pertofrane and others)

This medication is thought to be beneficial for panic, generalized anxiety and PTSD. As with other tricyclics, people do not generally develop a tolerance to it and it is not considered habit forming. One advantage of this medication is that it is reported to cause little to no drowsiness and weight gain is less.

However, it is not reported to help much with anticipatory anxiety and again, it can take weeks or months to have a positive effect. Alcohol must be completely avoided and it is said to increase sensitivity to the sun.

Nortriptyline (Pamelor, Aventyl)

This drug is reported to help panic, generalized anxiety and PTSD. Again, it is not reported to be much assistance in cases of anticipatory anxiety. It can take a long time to take effect and in the early stages blood tests are required regularly in order to establish the correct level of the medication. This medication can be used in pregnancy but not during the first three months and like other tricylics it increases sensitivity to the sun. It is said to cause less “jitteriness” than imipramine and less postural hypotension than some of the other tricylics.

Clomipramine (Anafranil)

This medication is recommended for use in control obsessive-compulsive disorder. It works by reducing the intensity and duration of symptoms and also lessens the associated anxiety. It is also thought to be as helpful as imipramine for panic attacks.

However, it is reported to have strong side effects. There are several conditions in which it is strongly contraindicated and it must be avoided during the last three months of pregnancy otherwise withdrawal symptoms may be observed in the baby when born.

As with imipramine, increased general anxiety is reported in the early stages and common side effects include headaches, feeling drowsy, dry mouth, insomnia and constipation. It is reported to have many of the same side effects of other tricyclics; in addition elderly people may experience confusion and memory impairment when taking it.

Amitriptyline (Elavil)

Amitriptyline is considered helpful for panic attacks, generalized anxiety and PTSD. It is said to be less likely to cause insomnia; indeed it is sometimes prescribed for people who are having trouble sleeping.

As with other tricyclics it is not of much assistance with anticipatory anxiety and can take a long time to take effect. It is supposed to have strong sedating effects which can impact upon productivity and concentration. Again its use in early pregnancy (and pregnancy generally is not recommended) is to be avoided and before breast-feeding. It has strong anticholinergic effects and induces sun sensitivity; again sleepiness, weight gain and dizziness are common.

Doxepin (Sinequan, Adapin)

This tricyclic is believed to be helpful for panic attacks and depression. It does little for anticipatory anxiety and again, response time can be long. Like amitriptyline, its sedating side effects can have an impact upon productivity and concentration in the day time. Side effects are similar to other tricyclics — anticholinergic effects, increased sun sensitivity, postural hypotension, weight gain and sweating.

So while this older style of antidepressants may be useful in some cases of anxiety, the evidence is that the side effects are many and there are some serious risks being discovered so their use is with caution. 

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