2.1 Tolerance (1)

Based on the evidence outlined in Article 1.3 above, we know that the prescription doses and duration were sufficient enough for Wayne to have formed tolerance. Further to the reference given on Page 13 of my first report, Professor Ashton has provided the following information:

“Tolerance and dependence can develop if benzodiazepines are used regularly for longer than 2-4 weeks.  There is no minimum dose, for example tolerance and dependence have been observed after the regular use of 2.5-5mg of diazepam.”

NB 1: We must also consider that the rate and degree to which tolerance forms is different for each individual and this is the reason why close monitoring is so important.

NB 2: It is possible to form tolerance on both long and short acting agents.

The fact that Wayne produced withdrawal symptoms upon reduction at our service in April 2001 confirms that he had developed tolerance.

NB: As outlined in my second report, dated 23rd December 2008, withdrawal and tolerance are interrelated because if a patient does not have tolerance, then there is no neuro-adaptation, and thus no withdrawals will occur.

Subsequently, the only question is when did he first develop tolerance and what were the signs.

Tolerance can be made apparent by the following signs:

1. Resurfacing and/or worsening of original symptoms
2. Failure of drugs to contain illness long term
3. Development of withdrawal symptoms during treatment (See Article 2.2)
4. Development of withdrawal symptoms upon reduction (See Article 2.2)

(1) Resurfacing and/or Worsening of Original Symptoms

2.1.1

The content of Dr. X’s patient file shows that Wayne was complaining of neck and back pain upon initial presentation on 30th June 2000 (See page 11 – Wayne’s hand written note).

2.1.2

The content of Dr. X’s patient file shows the following entry made on 19th July 2000 “Shoulder ache, muscle tension on neck - None” (See page 8).

NB: This is consistent with reports from Wayne upon presentation to our service saying that he experienced an initial settling of symptoms following the first 2 or so weeks of his treatment. Other symptoms that Wayne reported settled initially and then worsened again included his feelings of anxiousness and dizziness.

2.1.3

The content of Dr. X’s patient file does not contain Wayne’s handwritten note, dated 21st August 2000, however, I understand that it has been entered into the evidence (Evidence Koh A12-1) and that it reads as follows:

2.1.4

The symptoms in this handwritten note are consistent with reports from Wayne upon presentation to our service saying that after his initial settling of symptoms, he experienced a short period of little change, but following about 1.5 months of Benzodiazepine based treatment, he noticed that he had: (1) continuing symptoms, (2) worsening symptoms and (3) some new symptoms as well.

2.1.5

The continuing of symptoms is apparent in numbers 1, 2, 6, 8 in the above list.

2.1.6

The exception is that there appeared to be some improvement in 3a, 4 at this point in time. NB: Tolerance does not always form across all symptoms.

2.1.7

The worsening of symptoms is apparent in numbers 5, 9 in the above list.

NB: According to Dr. X’s patient file, Wayne’s initial complaint of neck and back pain had disappeared after about 2 weeks of treatment (See page 8), but the above list suggests that this had returned. Wayne’s other comment saying that the feeling of weakness in his legs momentarily came right, but then worsened again is of a similar pattern in that it improved initially and then worsened again.

2.1.8

The development of (notable) new symptoms is apparent in the listing of “Palpitations”. I note that there is no previous mention of this either in Wayne’s handwritten notes or in any of the other patient files prior.

NB: I can confirm that this is consistent with withdrawal type symptoms.

(2) Failure of Drugs to Contain Illness Long Term

2.1.9

The fact that Wayne showed an initial settling of symptoms followed by the return of certain other symptoms along with the development of new symptoms (See Articles 2.1.3 & 2.2.3) suggests that he had started to develop the early stages of tolerance following about 1.5 months of Benzodiazepine based treatment, and subsequently, this shows that the drugs were not achieving the desired result of containing Wayne’s symptoms long term.

2.1.10

I have been informed that Dr. X is claiming Wayne had made a full recovery as a result of his drug treatment whilst under his care. However, the Patient Questionnaire Form on page 2 of the O Medical Centre patient file shows that Wayne was still suffering from various symptoms including his original complaint of dizziness (Evidence Koh A6), as was the case when he presented to our service in April 2001.

2.1.11

Taking into consideration the above, and due to the fact that Wayne experienced withdrawal symptoms upon reduction (personally observed by myself), we can conclude that his body had neuro-adapted and therefore, we can also conclude that he had developed tolerance.

Conclusion: Wayne meets the DSM-IV-TR criteria for “Tolerance”.

2.2 Withdrawal (2)

Withdrawal can be made apparent by the following:

1. Worsening of original symptoms (frequency, intensity, nature) during treatment
2. Development of new symptoms during treatment
3. Worsening of symptoms (frequency, intensity, nature) upon reduction
4. Development of new symptoms upon reduction

(1) Worsening of Original Symptoms During Treatment

(Muscle Stiffness)

2.2.1

The worsening of original symptoms during treatment was apparent in the complaint of muscle stiffness. Wayne’s handwritten note (Evidence A12-1) shows that he experienced a worsening in muscle stiffness (See article 2.1.3) after this symptom initially settled (See page 8 of Dr. X’s patient file). I have been informed that Wayne began a course of massages from November 2000 at a local physiotherapy clinic in Saitama to help try and alleviate this.

2.2.2

Wayne’s handwritten note (Evidence Koh A26) shows that this muscles stiffness came to include a significant tightening in his jaw, which led to him not being able to close his mouth properly following about 4 ~ 6 months of Benzodiazepine prescriptions.

Also contained in this list was “pains in joints”. This is supported by the fact that after returning to New Zealand, Wayne consulted the Dental Department here at Taranaki Base Hospital and was diagnosed with Temporo Mandibular Disorder, or TMD.  

NB: In the Q & A document, between Mr. A and me, dated 19th December 2008, I said that I was unable to comment further on some of Wayne’s symptoms including the muscle stiffness. This is because further information was needed at the time in order to be able to make a more objective decision. However, now that I have had the opportunity to view the patient files firsthand, and to consider this in context, I can confirm that the muscle stiffness is consistent with withdrawal.

(2) Development of New Symptoms During Treatment

2.2.3

The content of Dr. X’s patient file (See page 29) shows the first 4 symptoms contained in Wayne’s handwritten note (Evidence Koh A26), as shown below.

NB: I understand that the above handwritten note was initially given to Dr. X only in partial form on 25th December 2000 at Wayne’s final consultation. I have been informed that, although, Wayne complained of all these symptoms verbally, he decided to add to the partial version of the list whilst waiting in the waiting room with the intention of showing it to Dr. X, or the nursing staff, in order to convey his condition more clearly. Wayne reports that he did not have the opportunity to show the completed list to Dr. X as intended, and that he showed it to Dr. M on 22nd January 2001 instead.

2.2.4

Symptoms of interest in the above list include; tinnitus, sensitive to heat (hypersensitivity), pulse rate (tachycardia), flushes, loss in sexual interest, feelings of detachment (emotional anaesthesia), pressure in chest, occasional stomach pains, jaw pain, joint pains. The content of all the previous patient files confirm that Wayne did not have these symptoms prior to commencing the Benzodiazepine regime. These symptoms are consistent with withdrawal type symptoms and/or side-effects.

2.2.5

The only symptom from (2.2.4) above that Wayne had prior to commencing the Benzodiazepine regime was tinnitus. The content of the STRC Hospital ENT patient file shows that Wayne complained of tinnitus following his initial vertigo attack in May 2000 (page 12). However, Wayne reports that this had rectified itself before his first consultation with Dr. X on 30th June 2000, which is supported by the fact that there was no mention of it again, either in Wayne’s initial handwritten notes to Dr. X, or indeed in Dr. X’s patient file either.

2.2.6

The fact that tinnitus developed for a second time, following 4~6 months of Benzodiazepines, is once again consistent with withdrawal type symptoms. Symptom escape (where symptoms of the original complaint resurface due to tolerance and lost drug effect) may also be suggestive.

2.2.7

The symptoms that were consistent with withdrawal and first developed during the course of Wayne’s treatment were most likely secondary to the development of tolerance. As mentioned in my second report, however, it is most likely that Wayne’s condition was due to a combination of these withdrawal symptoms together with other adverse effects, or symptom clusters, which is common in Benzodiazepine dependence. This is supported by Professor Ashton, who states the following:

“When tolerance develops, “withdrawal” symptoms can appear even though the user continues to take the drug. Thus the symptoms suffered by many long-term users are a mixture of adverse effects of the drugs and “withdrawal” effects due to tolerance.” (See Benzodiazepines: How They Work and How to Withdrawal. Prof. C. H. Ashton. Revised August 2002 – Chapter 2, Pages 2/10 of online version).

2.2.8

Further to my second report, dated 23rd December 2008 (which focused mainly on the possibility of breakthrough withdrawal symptoms occurring during treatment due to tolerance and oscillating plasma levels on short acting agents, such as Tofisopam), I would like to clarify that it is also possible for a patient to get “withdrawal” symptoms during treatment simply due to tolerance alone, even on long acting agents. This is because once a patient has developed tolerance; the same dose of Benzodiazepine may not exert the same effect, even if it produces the same plasma levels.

(3) Worsening of Symptoms Upon Reduction

2.2.9

As mentioned in my first report, Wayne met the criteria for withdrawal, which was made evident by the following symptoms. Some of these first emerged during the course of his treatment (See Article 2.2.3) due to tolerance and others appeared for the first time on reduction of his overall dose:

2.2.10

Worsening of symptoms (frequency, intensity, nature) upon reduction is apparent in numbers 5~14 in the above list, as explained below.

(5.Increased Joint Pains, 6.Tightening of Muscles)

2.2.11

Further to Articles 2.2.1~3 above / pg 17 of my first report, a GP recommended that he undergo a course of acupuncture to help assist with the additional muscle stiffness that he was experiencing upon reduction with Dr. John Yuan (Evidence Koh C10-3).   

(7.Worsening of Dizziness, 8.Worsening of Pulsating)

2.2.12

Further to page 17 of my first report, some of the first symptoms to worsen upon reduction included the worsening in dizziness and pulsating in temple areas.

NB: This is consistent with Dr. M’s observation during Wayne’s 2nd (planned) attempt at reduction on 1st March 2001 (See page 10 of O patient file).

(9.Worsening of Visual Disturbances)

2.2.13

Further to page 19 of my first report, Wayne was concerned about his worsening of visual disturbances, and subsequently, upon our advice he arranged a follow-up examination with Ophthalmologist, Dr. Kevin Taylor, who suggested that the staggered vision may have been due to the Benzodiazepines slowing down visual signals to the brain.

(10.Increase in Emotional Instability)

2.2.14

Further to page 17 of my first report, we referred Wayne onto Clinical Psychologist,  Alan Guy, for periodic consultations regarding the increase in emotional stability that he was experiencing upon reduction (Evidence Koh A18).

(11.Increased Palpitations, 12.Tightening in Chest, 13.Flushing)

2.2.15

Further to page 13 of my first report, Wayne complained that these symptoms, which first developed during the treatment (See Articles 2.1.3 & 2.2.3), worsened again upon reduction.

(14. Hypersensitivity)

2.2.16

Further to page 13 of my first report, Wayne complained of an increase in sensitivity to light and sound during the reduction process. Wayne reports that he often found TV programs with visual effects too overwhelming and the sound too loud compared with other normal people around him.

(4) Development of New Symptoms Upon Reduction

2.2.17

Development of new symptoms upon reduction is apparent in numbers 1 ~ 4 in the above list, as explained below.

(1.Tingling Sensation over Face)

2.2.18

As outlined on page 17 of my first report, Wayne experienced a tingling sensation over his face upon reduction (Paresthesia).

(2.Loss in Coordination)

2.2.19

As outlined on page 17 of my first report, Wayne experienced a loss in coordination, which is related to neuromotor dysfunction, and included arm and hand movements.

(3.Myoclonic Jerks)

2.2.20

As outlined on page 17 of my first report, Wayne experienced myoclonic jerks, which is a symptom of withdrawal observed in some people. (See Benzodiazepine Withdrawal: An Unfinished Story. Prof. C. H. Ashton. 1984, Page 9/13 of online version).

(4.Oily Smell in Body Odour)

2.2.21

As outlined on page 17 of my first report, Wayne experienced the sensation of emanating an oily smell in his body odor. This can be associated with an increase in hypersensitivity, where patients in withdrawal experience a heightened sensitivity to all sensations including hearing, sight, touch, taste and smell. (See Benzodiazepines: How They Work and How to Withdrawal. Prof. C. H. Ashton. Revised August 2002 – Chapter 3, Pages 7/22 of online version).

2.2.22

As outlined above, Wayne experienced the worsening of original symptoms and the development of new symptoms, which were consistent with withdrawal, both during the treatment (due to tolerance) and also upon reduction at our service.

Conclusion: Wayne meets the DSM-IV-TR criteria for “Withdrawal”.

2.3 Loss of Control (4)

2.3.1

The content of the O Medical Centre patient file shows that a reduction plan was put in place on 7th February 2001 (See page 10). In accordance with this reduction plan, Wayne attempted reducing his intake from 3 to 2 times a day from 1st March with a follow-up consultation directly after on 2nd March, which was probably scheduled to check on progress.

2.3.2

There is an entry on 2nd March recording the result of this attempt at reduction, as follows:

“(S) Pulsation on his temple (right-? not readable)

(O) Wondering if drug should be changed to 2 times (since the dizziness is increasing.)”

2.3.3

There is another entry in the patient file on 19th March, which reads; “Takes drugs 3 times / day”.

2.3.4

This provides a clear record that Wayne’s 2nd attempt at reduction (from 3 to 2 times a day), in accordance with Dr. M’s reduction plan, was unsuccessful because he had resumed in taking the doses 3 times daily.

2.3.5

There is another entry on 19th March stating “I am thinking of going off (the drugs) after return home”.

2.3.6

This supports Wayne’s statement saying that he made a 3rd unsuccessful attempt at stopping in late March 2001 after returning to New Zealand, but was unable to do so, and subsequently, sought help from Dr. Whitwell and later from our service.

Conclusion: Wayne meets the DSM-IV-TR criteria for “Loss of Control”.

2.4 Impact on Life (6)

2.4.1

The content of the STRC Hospital Neurology patient file says “Patient can continue ordinary work without any problem” (See page 17).

NB: This supports Wayne’s claim that he was still able to work in Japan, albeit on light duties, before the Benzodiazepine treatment began and during the early stages of the treatment.

2.4.2

The letter from Dr. Whitwell shows that following more than 6 months of Benzodiazepine exposure, Wayne ended up in a state where he was unable to work at all again for a period exceeding one year (Evidence Koh A7).

NB: Wayne was only declared fit enough to return to work again after the drugs had been removed and after he had recovered from the initial withdrawal phase of his dependency.

2.4.3

The two statements submitted by Wayne’s friends, Edward TeUa and Joseph Tait (who knew him well before, during and after his dependency problem), show that Wayne was suffering a loss in ability to socialize. Noted in these statements were aggressive tendencies; including an incident where Wayne stood up and made abusive comments to passengers on a shuttle bus in September 2000 and another when he became aggressive towards patrons at a café in late November, which was said to be out of character (Evidence Koh A14&15).

2.4.4

The statement submitted by Wayne’s mother shows that he was experiencing relationship difficulties. Noted in this statement was Wayne’s inability to communicate properly (in a way that was normally expected), inability to concentrate, extreme moodiness and mood swings, depression etc. Wayne reports that this instability caused his mother taking up smoking again for the first time in twenty years, which may also help to give some indication of the pressure that his condition was placing on their relationship at the time (Evidence Koh C4).

2.4.5

Wayne’s 1st statement (Evidence Koh A22) shows that he was experiencing difficulties with romance (See pages 12 & 15). Noted in this statement was Wayne’s loss in sexual interest, his tendency to say hurtful things and subsequent arguments with his girlfriend at the time (K).

NB: Wayne’s handwritten note (Evidence Koh A26) also notes contains loss in sexual interest.

2.4.6

Wayne’s 2nd statement (Evidence Koh A30) shows that he was experiencing a significant reduction in his ability to take part in recreational activities. Noted in this statement was the reluctance of a local gym to allow Wayne to become a member because he was still walking like a drunk and sometimes had to support himself by holding onto things (See Articles 22 & 25).

NB: Considering that Wayne was experiencing difficulty in walking, the social problems outlined above, and that he was suffering from both physical and psychological symptoms, it seems reasonable to conclude that he was also experiencing a loss in his ability to take part in normal activities.

2.4.7

As outlined above, Wayne experienced impairment on his ability to work, loss in ability to socialize, relationship difficulties, difficulties with romance, and a reduction in his ability to take part in recreational activities – showing a significant impact on his life.

Conclusion: Wayne meets the DSM-IV-TR criteria for “Impact on Life”.

2.5 Continued Use Despite Knowledge of Harm (7)

2.5.1

The content of Dr. X’s patient file shows that Wayne was the type of person who showed an ongoing awareness of his condition. This is apparent in his handwritten notes, both at first presentation and during the course of the treatment (See pages 11~13, 29).

2.5.2

The content of the STRC Hospital patient file shows that Wayne returned to the Neurology Department seeking a re-referral to another hospital in the quest for alternative treatment. This is consistent with showing awareness that the drug treatment under Dr. X may have been causing him harm.

NB: The timeframe of this re-referral request (13th Dec 2000) coincides with Wayne’s first reported attempt at reduction (late November) and his handwritten note (18th Dec 2000), which all occurred within about 3 weeks of one another.

2.5.3

The content of the O Medical Centre patient file shows that Wayne had a desire to reduce, which is made clear where it says “wants to taper medication” (See pg 10).

2.5.4

The content of the O Medical Centre patient file shows that Wayne and Dr. M had negotiated a reduction plan. In accordance with this plan Wayne attempted reducing from 3 to 2 times a day, but was unsuccessful (See Article 2.3 - Loss of Control).

NB: This supports the fact that Wayne was aware the drugs may be causing him harm, but continued to take them 3 times a day because he was unable to stop.

Conclusion: Wayne meets the DSM-IV-TR criteria for “Continued Use Despite Knowledge of Harm”.