Overload

TCAs - Tricyclic antidepressants

Category: Medicines

Type

Involuntary

Introduction and description

 

I have an entry for anti-depressants that are SSRIs, but TCAs act differently and thus need a separate entry. 

A TCA is a tricyclic antidepressant.

Despite their name they are used to treat

ADHD, anxiety disorders, obsessive-compulsive disorder (OCD), and panic attacks,  post-traumatic stress disorder (PTSD), eating disorders like anorexia nervosa and bulimia nervosa, certain personality disorders such as borderline personality disorder (BPD), Parkinson's disease, chronic pain, neuralgia or neuropathic pain, and fibromyalgia, headache, or migraine, smoking cessation, tourette syndrome,  irritable bowel syndrome (IBS), interstitial cystitis (IC), nocturnal enuresis, narcolepsy, insomnia, pathological crying and/or laughing [sic], chronic hiccups [sic], ciguatera poisoning, and as an adjunct in schizophrenia.

Other so called ‘Investigational uses’, which appear to include off-label prescribing, include – and this list is genuine and from Wikipedia:

  • Insomnia:
  • Urinary incontinence.
  • Cyclic vomiting syndrome
  • Chronic cough [sic]
  • Preventive treatment [sic] for patients with recurring biliary dyskinesia (sphincter of Oddi dysfunction)
  • Retching/dry heaving, especially after the ant-reflux procedure nissen fundoplication

Their action like many of the pharmaceuticals in this section can be hugely complex with multiple receptor activity.  But a large number have reuptake inhibitory activity and it appears to be this that mediates most of their side-effects, as well as their capability to produce hallucinations. 

 

And the number of hallucinations, out of body experiences and visions they produce is indeed extremely impressive; why bother with illegal mushrooms when your doctor can prescribe this lot legally [a cynical note has crept in here  - sorry]

Needless to say they are heavily abused and incorporated in a range of street drugs sold to people who have absolutely no idea what they are buying.

Side effects

If we take Wellbutrin as an example and use the information from eHealthme derived from Adverse Drug reports submiyted to SEDA an dthe FDA by doctors, we find first of all that quite a significant number of doctors have reported side effects:

On Jul, 18, 2015: 49,399 people who reported to have side effects when taking Wellbutrin are studied

 outcomes

The most common side-effects, again according to the reports are as follows

< 1 month

1 - 6 months

6 - 12 months

1 - 2 years

2 - 5 years

5 - 10 years

10+ years

Rash

Depression

Grand Mal Convulsion

Convulsion

Anxiety

Depression

Depression

Insomnia

Convulsion

Convulsion

Depression

Depression

Anxiety

Dizziness

Anxiety

Anxiety

Depression

Anxiety

Insomnia

Suicide Attempt

Anxiety

Nausea

Grand Mal Convulsion

Nausea

Grand Mal Convulsion

Convulsion

Fatigue

Insomnia

Dizziness

Dizziness

Insomnia

Pain

Headache

Intentional Overdose

Headache

Urticaria

Nausea

Headache

Dizziness

Hypertension

Insomnia

Tremor

Convulsion

Drug Ineffective

Drug Ineffective

Headache

Suicide Attempt

Suicidal Ideation

Weight Increased

Headache

Headache

Anxiety

Nausea

Pain

Dizziness

Nausea

Drug Ineffective

Insomnia

Type 2 Diabetes Mellitus

Emotional Distress

Suicidal Ideation

Headache

Fatigue

Depression

Suicidal Ideation

Suicidal Ideation

Drug Ineffective

Weight Decreased

Aggression

Tinnitus

Given that this class of drugs aims to treat depression and anxiety, it is interesting to note that the most common side effects are anxiety, depression, aggression, emotional distress and suicidal ideation.  Grand mal convulsions [epileptic fits] are also another side-effect worth noting.  Obesity and pain are probably the least of your worries.

If we now take another example, such as Mirtazapine, then again from eHealthme we find the following

Most common side effects by gender  :

Female

Male

Anxiety Completed Suicide
Nausea Depression
Depression Anxiety
Dyspnoea Confusional State
Fall Fatigue
Fatigue Nausea
Dizziness Dyspnoea
Headache Insomnia
Pain Agitation
Vomiting Suicide Attempt

and just to provide a comparative drug these are the most common side effects for Remeron

Most common side effects by gender  :

Female Male
Nausea Anxiety
Depression Nausea
Anxiety Depression
Pain Pain
Dyspnoea Fatigue
Fatigue Dyspnoea
Weight Increased Insomnia
Headache Weight Decreased
Diarrhoea Asthenia
Drug Ineffective Diabetes Mellitus

Death

 

If we now look at the figures for deaths - the ultimate spiritual experience- again using the eHealthme figures we find the following.  Adding up the figures this is over 1600 deaths from this class of drugs.  I leave it to you to add up the side effect figures!:

Amitriptyline - On Jul, 9, 2015: 5,783 people reported to have side effects when taking Amitriptyline hydrochloride. Among them, 76 people (1.31%) have Death.

Endep - On Jul, 25, 2015: 433 people reported to have side effects when taking Endep. Among them, 9 people (2.08%) have Death.

Elavil - On Jul, 21, 2015: 11,120 people reported to have side effects when taking Elavil. Among them, 192 people (1.73%) have Death.

Buproprion - On Jul, 26, 2015: 5,557 people reported to have side effects when taking Bupropion hydrochloride. Among them, 59 people (1.06%) have Death.

Clomipramine - On Jul, 29, 2015: 392 people reported to have side effects when taking Clomipramine hydrochloride. Among them, 4 people (1.02%) have Death.  [figures only available from 2007]

Zyban - On Aug, 8, 2015: 6,961 people reported to have side effects when taking Zyban. Among them, 87 people (1.25%) have Death.

Anafranil -  On Jul, 26, 2015: 3,477 people reported to have side effects when taking Anafranil. Among them, 35 people (1.01%) have Death

Desipramine - On Jul, 15, 2015: 114 people reported to have side effects when taking Desipramine hydrochloride. Among them, 2 people (1.75%) have Death.

Norpramine - On Jul, 27, 2015: 174 people reported to have side effects when taking Norpramin. Among them, 3 people (1.72%) have Death

Doxepin - On Aug, 3, 2015: 500 people reported to have side effects when taking Doxepin hydrochloride. Among them, 7 people (1.40%) have Death.

Wellbutrin - On Jul, 16, 2015: 49,378 people reported to have side effects when taking Wellbutrin. Among them, 416 people (0.84%) have Death.

Imipramine - On Jul, 30, 2015: 279 people reported to have side effects when taking Imipramine hydrochloride. Among them, 1 people (0.36%) has Death.

Tofranil - On Aug, 2, 2015: 1,344 people reported to have side effects when taking Tofranil. Among them, 15 people (1.12%) have Death.

Trimipamine - On Aug, 8, 2015: 598 people reported to have side effects when taking Trimipramine maleate. Among them, 6 people (1.00%) have Death.

Mirtazapine - On Aug, 8, 2015: 17,120 people reported to have side effects when taking Mirtazapine. Among them, 406 people (2.37%) have Death.

Nortriptyline - On Aug, 5, 2015: 988 people reported to have side effects when taking Nortriptyline hydrochloride. Among them, 16 people (1.62%) have Death

Pamelor - On Aug, 2, 2015: 2,064 people reported to have side effects when taking Pamelor. Among them, 25 people (1.21%) have Death

Vivactil - On Aug, 8, 2015: 136 people reported to have side effects when taking Vivactil. Among them, 1 people (0.74%) has Death

Remeron - On Jul, 31, 2015: 12,154 people reported to have side effects when taking Remeron. Among them, 270 people (2.22%) have Death.

Summary

Using the figures from the eHealthme web site, which are derived from Adverse Drug Reports submitted by doctors to the FDA and SEDA, the totals of deaths and side effects are as follows.  The figures only apply to the USA and were correct as at July 2015

Number of people suffering side effects: 118,572

Total number of deaths:  1,630

 

How it works

I was tempted at first to simply write "Who knows! if the drug companies don't know then I can't work it out!!", but one of the very clear mechanism by which these cause any number of symptoms not just hallucinations, is

Serotonin imbalance.

 

References and further reading

All the photos are by Katerina Plotnikova

Observations

 

 

 

The table below provides a summary of the number of hallucinations as of 2010, derived from the eHealthme website. 

The observations provide a more up-to-date figure, but you can follow the links to get both a current figure for the hallucinations and deaths as well as all the other side effects.

 

 

Observation no

Drug Name

No of hallucinations

005102

Amitriptyline /Endep

186

005102

Elavil

101

005104

Bupropion

220

005104

Wellbutrin

1235

005104

Zyban

221

005105

Clomipramine  

15

005105

Anafranil

36

 017332

Desipramine, Norpramine and Pertofrane

 1

005106

Doxepin

42

005107

Imipramine

12

005107

Tofranil

32

005108

Mirtazapine

235

005108

Remeron

474

005109

Nortriptyline  / Pamelor

33

017333

Trimipramine

4

 -

Vivactil / Protriptyline

 -
 

 

2,847

 

 

The following drugs have no entries for the reasons stated. 

  • Butriptyline (Evadene, Evadyne, Evasidol, Centrolese) is a tricyclic antidepressant (TCA) which has been used in Europe since 1974.  It is also a strong antihistamine and anticholinergic, moderate 5-HT2 and α1-adrenergic receptor antagonist, and weak serotonin reuptake inhibitor, with negligible affinity for the norepinephrine and dopamine transporters.  It has been abused but being European no figures exist on ehealthme.
  • Dosulepin  formerly known as dothiepin  and marketed under the brand names Prothiaden, Dothep, Thaden, and Dopress, is a tricyclic antidepressant that is used in several European and South Asian countries, as well as Australia, South Africa, and New Zealand. It is not used in the United States, hence no figures exist on ehealtme
  • EXP-561 is a drug which acts as a very potent serotonin, dopamine and norepinephrine reuptake inhibitor. It was developed in the 1960s and was suggested as a potential antidepressant but was never marketed.
  • Fencamine (Altimina, Sicoclor)  - is a dopamine and adregernic reuptake inhibitor.  No figures could be found.
  • Fezolamine (Win-41,528-2) is a drug which was investigated as an antidepressant in the 1980s. It acts as a serotonin, norepinephrine, and dopamine reuptake inhibitor, with 3- to 4-fold preference for the former neurotransmitter.   It was never marketed
  • Iprindole (Prondol, Galatur, Tertran), formerly known as pramindole, is a tricyclic antidepressant (TCA) used in Europe for the treatment of depression, used clinically since 1967.  Iprindole is a relatively weak inhibitor of the reuptake of serotonin and norepinephrine and instead acts predominantly as an antagonist of 5-HT2 receptors.  No figures as the product is not sold in the USA and eHealthme have no figures.
  • Lofepramine (brand name: Lomont (UK) Emdalen (ZA), Gamanil (IE, UK (discontinued)) & Tymelyt (discontinued)) is a third generation tricyclic antidepressant which was introduced in 1983 for the treatment of depressive disorders.  No figures as it is not sold in the USA
  • LR-5182 is a stimulant drug which acts as a norepinephrine-dopamine reuptake inhibitor, structurally related to the better known drug fencamfamine.   It was developed by the pharmaceutical company Eli Lilly in the 1970s, and researched for potential use as an antidepressant, although never marketed.
  • Medifoxamine (Cledial, Gerdaxyl) is an antidepressant which acts as a dopamine reuptake inhibitor  and agonist at the 5-HT2A and 5-HT2C receptors.   It was used mainly in France,  but was withdrawn following problems with hepatotoxicity.
  • Pridefine (AHR-1,118) is a drug which was investigated as an antidepressant in the late 1970s and early 1980s but was never marketed. It was a reuptake inhibitor of serotonin, dopamine, and norepinephrine, and also had some weak releasing activity.
  • Prolintane (Catovit) is norepinephrine-dopamine reuptake inhibitor .  It is used and I quote “for  elderly people to increase motivation and counteract the effects of senile dementia, anxiety and age-related cognitive decline, it can also be prescribed by doctors to help cure anxiety and stress related issues”.   It is mainly used in European countries and is legal world-wide.  As the eHealthme site is american I have no figures for this drug
  • Nomifensine (Merital, Alival) is a norepinephrine-dopamine reuptake inhibitor.  Nomifensine was investigated for use as an antidepressant in the 1970s, and was used as an antidepressant. The drug was not suitable for agitated patients as it made agitation worse.  Later studies in the 1980s concluded that there was potential for dependence and abuse of nomifensine, typically in patients with a history of stimulant addiction.  Nomifensine is now only rarely used as an antidepressant due to concerns about causing haemolytic anaemia, and problems with overstimulation and hyperthermia in overdose. It has been investigated for use in treating ADHD [sic].  Nomifensine has now been withdrawn from mainstream medical use. Some deaths were linked to the use of this compound
  • NS-2359 (GSK-372,475) is a serotonin-norepinephrine-dopamine reuptake inhibitor. It was under development as an antidepressant but was discontinued in 2009 when phase II clinical trials turned up 'disappointing results' and did not support further effort.  NS-2359 was also in clinical trials for the treatment of ADHD,  phase II having been completed in 2007. A trial exploring the effect of NS-2359 on cocaine-experienced individuals is currently ongoing.

Related observations