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Case reports have documented an increase in TS symptoms following the death of a parent, personal illness, birth of a sibling Eisenberg et al. Three long-term single case studies have investigated stress and TS and shown that increased stress increases tics, whereas reduced stress e. Other evaluations of substantial TS cohorts have found that increased stress or events which produce anxiety such as emotional trauma and social gatherings worsen tics Jagger et al.

Management can range from education to supportive reassurance to intricate pharmacological interventions, and ideally management should be multidisciplinary. At the outset it must be pointed out that education is mandatory and psychobehavioural methods and reassurance may well be sufficient for many patients, especially those with mild symptomatology. A variety of psychological techniques have been used in the treatment of TS. Subsequent literature has, however, shown inconsistent results using this method for review, see Evers and van de Wetering, Other psychological treatments which have proved useful in TS have included assertiveness training Mansdorf, , self-monitoring Billings, and cognitive therapy O'Connor et al.

Relaxation therapy Bergin et al. Evers and van de Wetering suggested a treatment model based on a specific tension reduction technique in which, instead of a tic which occurs in response to a specific sensory stimulus, the patient is taught a more socially acceptable alternative response which also reduces the sensory stimulus Evers and van de Wetering, By and large the author is not greatly impressed with psychological techniques for the treatment of the tics per se , as much of the documentation in the literature is anecdotal and, in her experience, results have not been particulary encouraging.

The neurobiology of TS has been thoroughly reviewed Messiha, ; Baker et al. These neurotransmitter systems include catecholamines dopamine and noradrenaline ; tryptophan and its metabolites serotonin, kynurenine, tryptamine , acetylcholine, the GABA amino acids glutamate, phenylalanine, p -tyrosine , trace amines e.

However, there have been relatively few post-mortem TS brains studied pathologically. Many parts of the brain have been invoked as abnormal in TS. Studies of eye movements have implicated basal ganglia dysfunction. MRI studies have implicated corpus callosum size and loss of normal asymmetrical predominance of the caudate. Much of the imaging and neurochemical data has been potentially conflicting. In fact, it has been pointed out that the efficacy of neuroleptics in treating tics see below was the main factor behind the prevailing theory of dysfunctional dopaminergic basal ganglia circuitry Robertson and Stern, Chemotherapy is, at present, the mainstay of treatment of the motor and vocal symptoms of TS, as well as some of the associated behaviours.

Thus, this communication will concentrate on pharmacological manoeuvres in the treatment of TS. Many studies and case reports will be reviewed, not only to demonstrate drug efficacy, but also to indicate the most favoured drugs and reasons for this. The pharmacological treatment of TS can be complex and may be difficult in many cases. It can be hampered by the fact that there have been relatively few double-blind medication studies and the controlled trials that there are have been conducted on relatively small numbers of patients. Combination strategies are often required according to which symptoms are being primarily targeted, and relatively few studies of these exist; augmentation strategies are also used for certain symptom groups.

Some patients, however, with multiple symptom profiles e. TS-plus appear refractory to many of the treatments. The most commonly prescribed medications for the motor and vocal tics have historically been the dopamine antagonists, but prescribing habits and efficacy vary widely. The most successful agents in this group are haloperidol, pimozide, sulpiride and tiapride. Other drugs such as clonidine, clonazepam and, more recently, risperidone are widely used but efficacy is still open to question.

Some drugs, including nicotinic agents, have some appeal but have had little exposure, while others such as clozapine and talipexole, have been found not to be useful. The most common DBTs have involved standard neuroleptics. Let us examine the drugs separately in detail. The neuroleptics are most often used as antipsychotic agents and are also misleadingly referred to as major tranquilizers. They are considered to act primarily by interfering with dopaminergic transmission in the brain by blocking dopamine receptors. Haloperidol, a butyrophenone derivative, is primarily a dopamine D2 receptor blocker Messiha, Seignot first documented its use in the treatment of TS Seignot, , but it has recently been shown that the patient previously had a frontal lobotomy Rickards et al.

Since then, however, it has been the most tried and tested medication, with many case reports of its successful use Caprini and Melotti, ; Challas and Brauer, ; Chapel et al.

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It has also, however, withstood the rigours of DBTs Connell et al. Monitoring of haloperidol treatment in a research setting has included measuring serum haloperidol levels which, with the low dosages in use, are remarkably small; this can be compared with both high doses and consequent high serum levels in patients with schizophrenia Singer et al.

In addition, in many studies, haloperidol has been shown to produce more side-effects when compared with other neuroleptics Ross and Moldofsky, , ; Singer et al. Side-effects of the neuroleptics in general will be discussed later. Borison and colleagues conducted placebo-controlled DBTs using fluphenazine and trifluoperazine which were as efficaceous as haloperidol, but with fewer side-effects.

In other studies, clonidine was shown to be equally as efficaceous as haloperidol, but did not produce adverse CNS side-effects. They also compared amantadine and benztropine in a crossover study. Amantadine was superior in treating the side-effects of haloperidol treatment in TS Borison et al. It does appear that if medications other than haloperidol are available they should be used as first-line agents, not because of increased efficacy, but because it now seems undisputed that haloperidol produces excessive adverse side-effects, as in controlled situations haloperidol produces more side-effects than other agents.

Pimozide is a diphenylbutylpiperidine derivative which posseses post-synaptic blocking activity with a preference for the dopamine D1 receptor Messiha, Ross and Moldofsky conducted a placebo-controlled DBT, in which both pimozide and haloperidol significantly decreased tic frequency in nine TS patients. Regeur and colleagues reviewed their management with 65 TS patients. Thirty-seven were treated with pimozide alone, five with pimozide and tetrabenazine and four with pimozide and clonidine. The dose ranges of pimozide were 0. Eighty-one per cent experienced a good clinical response without side-effects Regeur et al.

The active agents were more effective than placebo, but haloperidol was slightly more effective than pimozide. Adverse effects occurred more frequently with haloperidol versus placebo than with pimozide versus placebo, but the frequency was not significantly different for haloperidol compared with pimozide. Sallee and colleagues conducted a week placebo-controlled DBT, with double crossover comparison of pimozide and haloperidol therapy, and measured prolactin levels, tic severity and extrapyramidal side-effects EPSEs in 22 TS children and adolescents aged 7—16 years.

Pimozide was significantly superior to placebo, whereas haloperidol failed to reach significance. Haloperidol produced a 3-fold higher frequency of side-effects and significantly more EPSEs than pimozide. Pimozide responders demonstrated significantly raised prolactin compared with pimozide non-responders and haloperidol treated patients, suggesting that prolactin may be a marker for tic response to pimozide and conversely, a potential marker for haloperidol-related incidence of EPSEs Sallee et al.

Sallee and colleagues had previously reported results of cognitive testing in 66 TS patients, of whom one-third had comorbid ADHD, when pimozide was found to be significantly superior to haloperidol in improving cognitive functioning Sallee et al. Sandor and colleagues described a long-term follow-up study 1—15 years of 33 TS patients treated with pimozide 2—18 mg , haloperidol 2—15 mg or no drugs. Of importance is that no increased incidence of ECG abnormalities with pimozide were found Sandor et al. The substituted benzamides, selective D2 antagonists, have also become popular worldwide, excluding the USA and Canada, for the treatment of motor and vocal tics.

The most widely documented benzamide in the treatment of TS is sulpiride, first used by Yvonneau and Bezard in Yvonneau and Bezard, Subsequently, it has been extensively used and documented Robertson et al. The dose of sulpiride commenced at mg daily and increased to a limit of 1 g daily Robertson et al. George and colleagues undertook a week DBT with placebo-controlled crossover of fluvoxamine versus sulpiride, followed by single-blind combined therapy in 11 subjects with comorbid TS and OCD.

A case report of a year-old TS female Lipcsey, and a study including extrapyramidal hyperkinetic syndromes Klepel et al. Chouza and colleagues gave tiapride to 25 patients with various forms of dyskinesia for 3 months. A DBT of tiapride versus placebo showed significantly better results in the tiapride group. The forms of dyskinesia which responded best to tiapride included those of TS patients. An unequivocal, although minor, tiapride-induced parkinson syndrome was recorded in a few patients.

No instances of tiapride-induced dyskinesia or akathisia were seen Chouza et al. Eggers and colleagues conducted a placebo-controlled study on 10 children followed by a double-blind crossover study on 17 children using tiapride; tiapride was shown to have a positive therapeutic effect on tics and it had no adverse effects on neuropsychologically measurable cognitive performances in children. Neurophysiological parameters such as the EEG frequency analysis and sensory evoked potentials were not affected by tiapride; nor was the neurosecretory, hypothalamic—hypophyseal regulation of the sex hormones, thyroid stimulating hormone, growth hormone or thyroid hormone impaired.

The hyperprolactinaemia caused by tiapride's dopaminergic properties was moderate and restricted to the duration of therapy Eggers et al. Other benzamides which have also been used successfully in smaller numbers of TS patients include amisulpiride Trillet et al. In the UK remoxipride can only be prescribed on a named patient basis because of blood dyscrasias aplastic anaemia, cytopenia. To the best of the author's knowledge, there have been no reports of the use of the other benzamides such as raclopride and nemonapride for TS treatment.

Other neuroleptics such as the diphenylbutylpiperidine penfluridol Shapiro et al. In a few patients depot neuroleptics such as haloperidol Paolucci et al. Robertson, unpublished data have been used successfully. It has been pointed out that what exactly should be included in the definition of an atypical neuroleptic remains controversial, but the majority of investigators would agree that an essential requirement is a reduced risk of acute or subacute EPSEs Chappell et al.

Only three of these have been tried in TS patients, namely risperidone, clozapine and olanzapine. Risperidone, a benzisoxazole, has a higher affinity for 5-hydroxytryptamine 5-HT 2A receptors and lower dopamine D2 receptor binding than haloperidol Leysen et al. Several groups have recently reported success in treating TS symptoms with risperidone Bruggeman et al. At follow-up several months later, very few patients were still taking the drug. Interestingly, tics have also been reported following risperidone withdrawal Rowan and Malone, To date there have been only two reports of the use of clozaril in the treatment of TS.

Schmider and Hoff documented its use in an atypical TS patient with comorbid schizophreniform disorder Schmider and Hoff, Caine and colleagues conducted a unique study when they treated 12 patients with abnormal involuntary movement disorders, including seven with TS and others with Huntington's disease and atypical persistent dyskinesia, with clozapine in a placebo-controlled DBT.

Two dropped out due to complications. Overall, clozapine was found not to be effective; on the contrary, at doses of 50— mg clozapine was actually associated with transient increased tics. There were also, however, serious unacceptable side-effects Caine et al. Much later, McDougle and colleagues studied 10 OCD patients who were treated with clozapine and it was found to be ineffective McDougle et al. There have, however, been two case reports of the beneficial use of clozapine in tardive TS see below Kalian et al. In the latter report, the patients were treated with a combination of clozapine and propanolol, or clozapine and tetrabenazine Kalian et al.

Bhadrinath documented the successful use of olanzapine in a year-old TS girl with coprolalia and SIB. She had been treated unsuccessfully with haloperidol, pimozide and risperidone; all were discontinued either due to poor control of TS symptoms or unacceptable side-effects. The patient was started on olanzapine 5 mg daily which was raised to 10 mg after 1 week.

Over 9 weeks of treatment partial control of tic symptoms was achieved. Increased appetite lasted for 4 weeks and drowsiness improved when the medication was taken at night Bhadrinath, There are other atypical neuroleptics such as sertindole [Serlect, Serdolect now withdrawn from the UK market ] and quetiapine Seroquel , but to the best of the author's knowledge there have been no publications documenting the use of these drugs for the treatment of TS. Neuroleptics are useful in the treatment of TS as has been shown, but unfortunately are often associated with unacceptable side-effects.

The side-effects will be discussed in detail as they are not only important, but may be subtle, unusual and somewhat different to those seen in other conditions. Sixteen groups of side-effects are described in the following section. However, none of 46 TS cases were reported to have acute dystonic reactions with pimozide Regeur et al. It may be helped by neuroleptic dose reduction and withdrawal Barnes and McPhillips, ; Kurlan, a , or prescription of propanolol George et al. Sedation has been reported with pimozide Regeur et al. This is important as individuals with TS have been shown to be particularly prone to depression Robertson et al.

This may be dose related and thus treated by reducing the dose Kurlan, a , by discontinuing the drug Robertson et al. Tardive dystonia can occur occasionally after short-term treatment with low doses British National Formulary, Tardive dystonia has been reported with haloperidol Singh and Jankovic, while TD has been reported in one patient treated with sulpiride Eapen et al.

This latter case was unusual, as sulpiride has actually been successfully used in relieving symptoms of TD Haggstrom, ; Gerlach and Casey, ; Quinn and Marsden, ; Schwartz et al. To put this into context, in a series of 46 TS cases treated with pimozide Regeur et al. Treatment of TD and tardive dystonia can be difficult, but manoeuvres include reduction and eventual stoppage of the neuroleptic Miyasaki and Lang, , prescribing a combination of clozapine and clonazepam Shapleske et al.

Yassa and Ananth reviewed the efficacy of lithium therapy in the treatment of TD. A few well-designed studies indicate that lithium is useful in certain TD patients and that the plasma lithium level may be related to the therapeutic response Yassa and Ananth, Mikkelson and colleagues described 15 TS patients who developed school and work avoidance syndromes when treated with low dose haloperidol mean 2.

The phobic symptoms disappeared completely with discontinuation or reduction of the haloperidol dose Mikkelson et al. It was suggested that tricyclic antidepressants TCAs may have a therapeutic or indeed prophylactic effect Linet, Others, however, have suggested that the syndrome may actually be one of the many faces of neuroleptic-induced akathisia Heiser and Sramek, , while Munro suggested that it was a variant of depression Munro, and Bruun suggested that it is always associated with dysphoria Bruun, This is important as TS children have been demonstrated to be more phobic than controls with chronic tic disorder Spencer et al.

These patients respond to the antiepileptic drug, primidone, which suggests that they are probably partial seizures Bruun, It must be borne in mind, however, that the aetiology of weight gain is not fully understood. One strategy for counteracting the weight gain is by a strict diet and exercise programme Kurlan, a. This side-effect is probably related to its calcium channel blocking activity Messiha, As many TS patients require more than one medication, the physician must always be aware of the potential difficulties of using drugs in combination with pimozide because of the effects on the ECG and therefore the heart.

These include, for example, the reporting of sinus bradycardia with the combination of pimozide and fluoxetine Ahmed et al. Galactorrhoea has also been subsequently reported George et al. In the author's clinical practice in adult psychiatry, patients receiving sulpiride have had particulary high prolactin when they have had these three side-effects. Endocrine dysfunction such as impotence has also been reported with pimozide Ananth, It is basically an idiosyncratic reaction to neuroleptics characterized by muscular rigidity, fever, autonomic dysfunction, labile blood pressure, sweating, urinary incontinence, fluctuating level of consciousness, leucocytosis and an elevated serum creatine phosphokinase level the latter being brought about by rhabdomyolysis, i.

It affects males more than females, and patients between the ages of 12 and 78 years with NMS have been described. Most of the affected patients have had psychiatric diagnoses, but cases of NMS with narcolepsy, Huntington's and Parkinson's disease have also been documented. The neuroleptics most implicated are haloperidol and depot fluphenazine Levenson, ; British National Formulary, NMS has been reported with metoclopramide.

Successful treatments include essential discontinuation of the neuroleptic and prescription of drugs such as dantrolene, bromocriptine and amantadine Levenson, ; Jee, ; British National Formulary, Differential diagnosis includes severe dystonic reactions. One of the major aetiological theories is central dopaminergic blockade, although the exact underlying mechanism remains unclear Levenson, Neuroleptics implicated include chlorpromazine Klawans et al.

Tetrabenazine, a benzoquinolizine derivative, which depletes presynaptic storage of monoamines and blocks post-synaptic dopamine receptors, was initially used as an antipsychotic drug in Jankovic and Beach, and then succesfully in tic and hyperkinetic disorders Pakkenberg, ; Sweet et al. Jankovic and colleagues have used tetrabenazine for some time Jankovic et al. There have been some suggestions that tetrabenazine plus a dopamine antagonist, which acts post-synaptically, could be used together, as they may have a more lasting effect and fewer side-effects, because both drugs can be given in lower doses Fog and Regeur, More commonly recognized side-effects of tetrabenazine include depression Jankovic and Beach, ; BNF, , drowsiness, fatigue, parkinsonism, insomnia, nervousness, anxiety and akathisia Jankovic and Beach, In its favour, it has not been reported to cause TD Jankovic and Beach, Piquindone is a pyrroloisoquinoline derivative with D2 receptor antagonist properties Messiha, Uhr and colleagues treated four TS patients with piquindone.

All four experienced clinically obvious reductions of tics; motor tics responded at lower doses than vocal tics. Sedation that decreased over time was the only adverse effect and therefore piquindone produced therapeutic effects without disabling side-effects. All patients expressed a strong subjective preference for piquindone over haloperidol Uhr et al. To the best of the author's knowledge this agent is not licensed for use. Inosine has been used traditionally in the treatment of viral infections Reynolds, , has some immunomodulation properties Grieco et al.

Side-effects of inosine include transient nausea and vomiting Reynolds, and reversible increases in serum and urinary uric acid British National Formulary, Pergolide is a dopamine agonist with its agonist properties both at D2 and, to a lesser extent, at D1 receptors, and is used mainly in Parkinson's disease Reynolds, Lipinski and colleagues used pergolide in 32 TS patients aged 17—19 years in a 6-week open-label fixed-flexible dosing schedule.

Abrupt withdrawal of pergolide may precipitate hallucinations and confusion Reynolds, Amantadine, another dopamine agonist which also has antiviral properties, has modest effects when used in Parkinson's disease, but not drug induced extrapyramidal symptoms Reynolds, ; British National Formulary, To the best of the author's knowledge there is only one publication of its use in TS in which it was found not to be useful Walsh et al. Selegiline is a dose-dependent selective irreversible inhibitor of monoamine oxidase, type B, which is another dopamine agonist Reynolds, The main use of this agent is in the treatment of Parkinson's disease Reynolds, ; British National Formulary, The design included two 8-week treatment periods separated by a 6-week washout period.

Fifteen subjects completed the study. The primary analysis revealed, from the DuPaul Attention Deficit Hyperactivity Scale, no statistically significant beneficial effect of selegiline. However, further post hoc analyses revealed that the effect of selegeline in the first period was substantial.

There was also a marginally statistically significant beneficial effect of selegiline on the motor tics as evidenced by the YGTSS total score. Some patients, however, had an increase in tics Feigin et al. Talipexole is a new dopamine agonist that is under investigation for use in Parkinson's disease and schizophrenia Reynolds, The drug was poorly tolerated because of clinically significant sedation and dizziness.

Tics did not improve at tolerable doses Goetz et al. To the best of the author's knowledge this drug is not licensed for use in patients with TS. Braun and colleagues used a selective D1 dopamine receptor autoagonist, SKF , in patients including TS individuals, and no consistent changes of tics could be discerned Braun et al.

To the best of the author's knowledge this agent is not licensed for use in patients with TS. Clonidine is conventionally used as an oral preparation, but can also be used as a transdermal patch Dillon, ; Gancher et al. Clonidine is not licensed in the UK for the treatment of TS, although the BNF sanctions its use British National Formulary, ; its main indications are migraine, menopausal flushing and hypertension.

Although many clinicians worldwide now use clonidine, its effectiveness for the motor and vocal tics of TS has been questioned Goetz, For hypertension, the maximum daily dose can be 1. There have been several DBTs which have shown clonidine to be superior to comparator agents McKeith et al.

However, their profile of response is often variable, with behavioural symptoms appearing to show the most consistent improvement. Maximal benefit may not be evident for 4—6 months. A minority of patients do not respond and a few worsen on clonidine Leckman et al. Shapiro and colleagues conducted an open trial of clonidine and neuroleptics in patients with TS. Neuroleptics resulted in greater improvement across the range of symptoms in a larger proportion of patients than did clonidine Shapiro et al.

Leckman and colleagues treated 13 TS patients with clonidine 0. There was significant improvement in motor and phonic tics, as well as in associated behaviour problems, and there were no serious side-effects. Tolerance to clonidine did not develop Leckman et al. Goetz and colleagues evaluated 30 TS patients during a 6-month placebo-controlled crossover study of clonidine.

Videotapes were obtained at each 3-week visit and were evaluated randomly at the end of the study for distribution, frequency and severity of motor and vocal tics. Quantifiable psychometric examinations were also performed. Clonidine did not significantly reduce motor tics, vocalizations or behaviour. The effect of a low dose was no different from that of a high dose, children's responses were no different from adults', and those also receiving neuroleptic agents showed the same lack of efficacy as seen in patients on no other medication Goetz et al.

Twenty-four subjects took clonidine and 23 placebo. Forty individuals 21 clonidine, 19 placebo completed the week trial. Clinical ratings of tic severity improved for both groups. The magnitude of response was greater in the clonidine group. Thus, it appears that clonidine improves tics and ADHD and may also exert beneficial effects on the behavioural abnormalities, perhaps more so than on the motor and vocal tics Cohen et al.

Side-effects of clonidine important in TS include sedation, dizziness, depression, bradycardia, nocturnal unrest and euphoria, and sudden withdrawal can lead to a hypertensive crisis British National Formulary, It has been recommended that ECG, blood pressure and pulse baseline, in addition to regular monitoring, should be carried out if clonidine is used Taylor et al. In the author's clinic, however, only blood pressure and pulse are regularly monitored.

Chappell and colleagues conducted an open-label study of guanfacine in 10 children with TS plus ADHD, aged 8—16 years. The duration of follow-up was 4—20 weeks and the majority of patients were treated with 1. Standardized ratings of tic severity and ADHD symptoms were obtained. Blind Continuous Performance Tests were performed at baseline and at two follow-up intervals in eight subjects.

Guanfacine was associated with significant decreases in both commission and omission errors on the Continuous Performance Test. In addition, guanfacine caused a significant decrease in severity of motor and phonic tics. The most common side-effects were transient sedation and headaches Chappell et al.

The use of stimulants such as methylphenidate Ritalin, Ritaline, Rubifen , dexamphetamine Dexamin, Dexidrene, Dextrostat and pemoline Cylert, Dynalert, Volital in children with TS and ADHD has long been controversial Robertson and Eapen, , as they may worsen the tics, while improving the hyperactivity and concentration. This was felt to represent an absolute contraindication, but recently cautious use of these agents in this context has been advocated Freeman, Chronic motor tics and TS were exclusionary criteria.

All subjects were medication free for 3 weeks before the study. These adverse effects were often subtle and transient, and they usually occurred only on one drug. This necessitated discontinuation in only one case. Dexamphetamine tended to produce more compulsive behaviours, which were also more likely to resemble clinical OCD, than did methylphenidate. Abnormal movements and compulsive behaviours tended to co-occur on methylphenidate only Borcherding et al.

Gadow and colleagues studied 11 prepubertal hyperactive boys with tic disorder who received placebo and three doses of methylphenidate 0.

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Methylphenidate also reduced the occurrence of vocal tics in two settings. None of the motor tic measures revealed drug effects. On an operationally defined minimal effective dose, only one boy experienced motor tic exacerbation Gadow et al. Gadow and colleagues also studied 34 prepubertal children with ADHD and tic disorder who received placebo and three doses of methylphenidate twice daily for 2 weeks, each under double-blind conditions. However, these changes in motor tic frequency were not perceived by care providers as a worsening in the severity of the child's tic disorder.

Most dose—response relationships were linear, but the mean minimal effective dose was 0. Castellanos and colleagues conducted a 9-week placebo-controlled crossover DBT in 20 subjects in three cohorts, evaluating the effect of methylphenidate and dexamphetamine on tic severity in boys with ADHD and TS. Fairly high doses of methylphenidate and dexamphetamine in the first cohort resulted in significant increases in tic severity which were sustained on higher doses of dexamphetamine, but which attenuated on methylphenidate.

Fourteen of 20 subjects continued stimulant treatment for 1—3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases Castellanos et al. It has been suggested that when treating ADHD with stimulants, controlled release preparations and the adjunctive use of clonidine are helpful to extend stimulant effects and control the adverse effects Carrey et al. Clinicians have been successfully using a combination of clonidine and stimulants safely, for many years, to treat children with ADHD; it has been suggested that clonidine both works synergistically with stimulants to reduce behavioural symptoms, and helps with the initiation of sleep Popper, Consequent on three deaths reported in children receiving the combination, Popper carefully goes through all the evidence, and ends by suggesting that the deaths were probably not in fact due to the combination Popper, He very carefully thereafter considers the safety and sense of the combination, providing valuable guidelines for the clinician.

In the UK pemoline has been withdrawn from the market. Side-effects of the stimulant include dependence, psychotic states and growth retardation British National Formulary, Several markers for ADHD were shown to improve significantly after treatment with desipramine, and desipramine was always superior to clonidine. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not with standardized tic severity ratings.

Clonidine did not significantly alter tic severity with any measure Singer et al. Problems such as acute collapse and sudden death have, however, been reported with the use of desipramine in children Riddle et al. The main problem with the drug, however, is the side-effect profile e. In the author's experience, it is therefore not first choice. OCD is generally now thought to be unresponsive to psychodynamic psychotherapies, but it does respond to behaviour therapy, especially exposure and response prevention, and to medications such as clomipramine and the SSRIs Greist et al.

By and large, the doses given for depression are lower e. Fluoxetine and fluvoxamine have been documented most frequently in TS. Delgado and colleagues described a year-old man with TS who presented for treatment of OCD symptoms. Fluvoxamine worsened tics, led to coprolalia and did not help the OCD. Double-blind sequential discontinuation of fluvoxamine and pimozide confirmed that pimozide alone reduced only tics and the combination of fluvoxamine and pimozide was required for the improvement in OCD Delgado et al. Five of the 10 patients were responders. Fluoxetine was well tolerated, with adverse effects including behavioural agitation or activation in four patients and mild gastrointestinal symptoms in two Riddle et al.

Data were therefore analysed on 26 patients 13 children, 13 adults who were treated for 3—8 months. Fluoxetine therapy, however, was associated with a trend towards some improvement in tic severity, attentional abilities and social functioning Kurlan et al. McDougle and colleagues conducted a retrospective case-controlled analysis and evaluated fluvoxamine in 33 patients with OCD and a comorbid tic disorder, and 33 patients also with OCD but without a comorbid tic disorder.

McDougle and colleagues then undertook a study involving 62 patients with a principle DSM diagnosis of OCD and gave placebo for a week followed by 8 weeks of fluvoxamine in identical capsules. There had been no 1-week placebo responders. Thirty-four patients were refractory to fluvoxamine and were then entered into a 4-week double-blind placebo-controlled 2 mg haloperidol addition phase.

Haloperidol was not useful in treating OCD symptoms in the absence of tics. Fluvoxamine blood levels were not related to treatment response McDougle et al. Fluvoxamine George et al. Side-effects of the SSRIs include gastrointestinal side-effects diarrhoea, nausea and vomiting, which are dose related , headache, restlessness and anxiety; they do not cause weight gain British National Formulary, A DBT of diazepam a benzodiazepine versus placebo at 2 mg t. Whether or not this is due to a direct action on TS symptoms or is merely an anxiolytic effect is not clear.

There are, however, problems with long-term prescription of benzodiazepines including addiction and tolerance. Gonce and Barbeau first reported the successful use of clonazepam in seven TS patients Gonce and Barbeau, , followed by Dion and Chouinard Dion and Chouinard, , In general, it was felt that clonazepam was well tolerated and produced no TD. Drtilkova and colleagues compared clonazepam and clonidine in 20 children mean age 11 years , 14 with chronic tic disorder and six with TS. Clonazepam was significantly superior to clonidine and produced fewer side-effects Drtilkova et al.

Merikangas and colleagues conducted a single-blind investigation of 20 TS patients. As TS patients had previously been reported to have high red blood cell choline levels, red blood cell choline was measured. Patients with high red blood cell to plasma choline ratios responded significantly better to clonazepam than to haloperidol, and the clonazepam responders were significantly more likely to have a family history of TS or tics Merikangas et al.

Jankovic and Rohaidy reported that TS patients with mild symptoms improved with clonidine or clonazepam, whereas those with more severe symptomatology required fluphenazine, pimozide, haloperidol or tetrabenazine Jankovic and Rohaidy, On the other hand, clonazepam-induced TS symptoms in a year-old subject with hyperexplexia or abnormal startle response have been described Gillman and Sandyk, Clonazepam has also been used to treat tardive Tourette-like syndrome Kuniyoshi et al.

Side-effects of clonazepam important in TS include drowsiness, fatigue, dizziness, paradoxical aggression, irritability and mental changes British National Formulary, Mondrup and colleagues evaluated progabide a GABA receptor agonist in 17 patients with hyperkinetic movement disorders, including four with TS. Others have also suggested its use Fog and Regeur, It has been suggested that the pathophysiology of TS may be linked to a relative imbalance between cholinergic and dopaminergic activity within the striatum and that nicotine may alter this imbalance Dursun and Reveley, Animal experiments in the late s and early s demonstrated that nicotine potentiated haloperidol-induced catalepsy and reduced locomotor activity Manderscheid et al.

At around the same time, there was a case report that chewing nicotine gum reduces tics Brill, Devor and Isenberg reported a male TS patient whose symptoms reduced markedly when he smoked cigarettes Devor and Isenberg, In open studies involving small numbers of TS patients who were being treated with haloperidol, the frequency of tics was reduced significantly during a min nicotine gum Nicorette chewing period and the hour afterwards, suggesting once again that nicotine appears to potentiate the effects of haloperidol Sanberg et al.

In addition, many discontinued the gum because of side-effects, especially nausea and a bitter taste in the mouth Sanberg et al. Subsequent DBTs suggested that nicotine markedly potentiated haloperidol effects in treating TS and showed lesser effects on symptoms when used alone; placebo gum had no effect McConville et al. Mainly because of the unacceptable side-effects of gum, transdermal nicotine patches TNP were subsequently used Silver and Sanberg, ; Dursun et al.

Other side-effects of TNPs include headache, light-headedness, sweating, tremor and sleep disturbances Davila et al. Nicotine is also available as a nasal spray and an inhaler is under development Benowitz, ; to the best of the author's knowledge, neither of these applications has been used in TS. A nicotine antagonist, mecamyline marketed as an antihypertensive agent in the USA , was prescribed in 13 TS patients. Improvements were noted in tics, mood, irritability and aggression Sanberg et al.

It does appear that agents acting on the nicotine receptors may well be useful in the treatment of TS, especially when used as an augmenting agent to neuroleptics. More research, however, is needed in the area. Walsh and colleagues reported tic, irritability and compulsive symptom reduction with Verapamil Cordilox, Securon, Univer, Verapress; 20 mg t.

After a suggestion that nifedipine augments haloperidol in the treatment of TS, the successful combination of nifedipine and haloperidol in treating a patient with TS was reported Alessi et al. Micheli and colleagues evaluated seven TS patients aged 12—31 years, before treatment, after 1 month on placebo, after a single 10 mg nifedipine dose three subjects and monthly while on flunarizine 10—15 mg mean dose 13 mg.

None of the patients receiving nifedipine improved, but treatment with flunarizine significantly decreased both motor and phonic tic severity and frequency in all but one patient. Adverse effects occurred in four patients and included mild transient headaches, depression and bradykinesia Micheli et al. As there is some evidence that tic-like movements in animals such as head shakes and wet dog shakes are blocked by buspirone Handley and Dursun, , buspirone was tried and found to be useful in a patient who was refractory to other treatment Dursun et al.

Botulinum toxin injections were pioneered by Scott and colleagues Scott, ; Scott et al. They have been used for some time in focal dystonia Jankovic and Brin, and oral—lingual dyskinesia Ludlow et al. More recently they have proved useful in TS, targeting the symptoms of blepharospasm, neck and facial muscles Jankovic, ; Jankovic and Hallett, ; Poungvarin et al. Scott and colleagues reported on a year-old boy with severe coprolalia, OCD and ADHD who was considerably improved by unilateral vocal cord injections of botulinum toxin; not only was his coprolalia improved, but also the premonitory sensations that were associated with the vocal tics and coprolalia Scott et al.

He was injected with 3. His therapeutic response was excellent and not only reduced coprolalia, but also aided the general symptoms Trimble et al. On the other hand, Chappell and colleagues treated two males with botulinum toxin, both of whom had frequent and forceful tics involving a specific body area shoulder in one patient, lower thigh in the other ; an injection of botulinum toxin was given into these areas.

Neither patient had a reduction of tics or premonitory urges Chappell et al. Early work by Sandyk reported the successful use of naltrexone, naloxone and oxycodone on TS symptoms Sandyk, a , b ; Sandyk et al. Using a self-report scale, subjects reported a significant reduction of tics after treatment with naltrexone when compared with placebo. An improvement in the Trail Making B test, which is a measure of attention and visuomotor sequencing and planning, occurred after receiving naltrexone when compared with placebo or propoxyphene Kurlan et al. Pentazocine has also been reported as a useful drug Bazire, Meuldijk and Colon reported the case of a man whose TS symptoms responded to methadone after he had not responded to many traditional drugs Meuldijk and Colon, McConville and colleagues reported two TS patients who responded to the sequential use of opioid agonists and antagonists.

Risks with opioids are the addiction potential and the risk of tic exacerbation after sudden withdrawal McConville et al. The use of lithium in TS is not common. Few have documented the usefulness of lithium in a small number of TS patients Erickson et al. Kerbeshian and Burd described 13 boys with TS some of whom also had bipolar disorder; interestingly, when they were treated with lithium, the tic symptomatology improved in seven; blood levels ranged between 0.

The use of lithium, however, was not useful in controlling tic symptomatology in other cases Borison et al. Cholinergic modulating drugs such as physostigmine Stahl and Berger, , have proved useful, while others such as dimethylaminoethanol Deanol; Finney et al. On the other hand, cases have been reported where carbamazepine has reduced the TS symptoms Lutz and Feldman, An early study by Consroe and colleagues suggested that cannabidiol may be useful in dystonic movement disorders Consroe et al.

Sandyk and Awerbach then described three TS patients who had incomplete responses to conventional anti-TS medications and who then reported a significant reduction in both motor and vocal tics following recreational use of marijuana; the authors, however, note that the patients may have used marijuana to reduce the stress and anxiety that occurred secondary to TS, as all three reported reduced anxiety when using marijuana Sandyk and Awerbach, Moss and colleagues then suggested that cannabinoids may increase the effectiveness of neuroleptics in TS Moss et al.

Hemming and Yellowlees reported a year-old man who failed to respond to either haloperidol or pimozide, but who, several years later, found that his nightly intake of marijuana rendered him absolutely symptom free Hemming and Yellowlees, In the author's clinical experience several patients have reported a reduction in symptoms with the recreational use of marijuana.

It has also been documented, however, that cannabis has no effect on tics and increases the individuals inner tension Meuldijk and Colon, Certain drugs may be helpful in reducing the next-day effects of sleep deprivation such as melatonin. A preliminary study using melatonin in multidisabled children and early results in TS and ADHD are promising, with no significant side-effects Freeman, Several combination strategies have been used in TS including nicotine and haloperidol Silver and Sanberg, , and nicotine and sulpiride Dursun and Reveley, ; recently, the safe use of pergolide and both stimulants and clonidine has been reported Lipinski et al.

Kurlan, however, cautions that an acute parkinsonistic syndrome may be induced by the combination of a SSRI and a neuroleptic in adult TS patients Kurlan, Budman and colleagues have reported the successful use of the antiviral agent acyclovir Budman et al. These suggested medications have only been used in a small number of patients with very specific indications; results are still to be replicated in other laboratories and the treatments assessed in controlled studies in larger samples of patients.

Based on evidence implicating abnormal gonadotrophic functioning in TS, Sandyk and colleagues studied luteinizing hormone, follicle stimulating hormone, luteinizing hormone releasing hormone and testosterone; abnormalities suggested a hypothalamic-mediated luteinizing hormone releasing hormone deficiency. The antioestrogenic agent clomiphene citrate Clomid was successful in treating TS symptoms Sandyk et al. Peterson and colleagues reported the first use in TS of the non-steroidal androgen receptor blocking agent flutamide Eulexin, Fugerel.

One male and one female underwent open trials of the drug and a second male participated in a placebo-controlled crossover DBT. The improvement was sustained in the woman during daily flutamide ingestion and in one of the men during intermittent use. The symptoms of one of the men became refractory to treatment after 5 weeks of flutamide and the woman became depressed and had protracted diarrhoea during her treatment Peterson et al. One of the most novel recent treatments of TS has been laser therapy in Russia. Bondarenko and colleagues reported successful low-intensity infrared laser irradiation of blood, used to correct the antioxidative system in TS.

Index patients receiving laser therapy received lower doses of neuroleptics in contrast to controls no laser therapy who required higher neuroleptic doses Bondarenko et al. This of course is interesting, but must be viewed as experimental at this stage and is not used or advocated by experts, including the author. Wu and colleagues treated TS patients with acupuncture in China. The success rate was The cure rate in children aged 11—15 years was markedly higher than in children aged 6—10 years. Although fascinating, once again this is a single report and experts in the field, including the author, do not use this method.

Jankovic and Rohaidy documented their experience with TS patients. Most patients required a trial of more than one medication before a satisfactory improvement was reached. In summary, clonazepam and clonidine were tolerated relatively well, but only one-third had an excellent response. Pimozide, fluphenazine and tetrabenazine seemed most effective but were associated with more adverse reactions. Haloperidol had the highest incidence of side-effects.

Fulton and colleagues surveyed TS subjects who replied to a mailed questionnaire. The most commonly prescribed medications were reported to be haloperidol, pimozide, clonidine and benztropine Cogentin which was taken in conjunction with other medications. TS is probably a heterogeneous condition, from an aetiopathological, genetic, clinical phenomenological and psychopathological point of view.

To summarize, and in the author's opinion taking into account the literature and personal experience , there is no doubt that ADHD is very common in TS, even in mild cases. It is thought that, in time, it will be clear that there is a specific type of ADHD which is peculiar to TS, which is phenomenologically different from that in pure ADHD, but it is unclear as to whether or not this has treatment implications. In the author's opinion, the depression in TS is highly likely to be multifactorial in aetiology, highlighting the importance of a full psychiatric history and mental state examination in each patient.

The anxiety, personality disorders and other behavioural problems are often seen in TS clinics and may be due either to the comorbidity with ADHD or to referral bias. Certainly, the majority of the patients in the author's clinic usually have multiple pathology, although it is recognized that as it is a specialist clinic, it probably attracts patients who are more difficult to manage. Many neurotransmitters have been implicated as malfunctioning in TS.

As can be seen, the medications used to treat the various TS symptoms differ in their receptor affinity profile and indeed their efficacy. The most tried and tested medications for the motor and vocal tics remain the dopamine antagonists, with haloperidol, pimozide, sulpiride and tiapride receiving most attention. The new atypical neuroleptics such as risperidone and olanzapine have appeal and deserve further research; more DBTs are certainly needed. Clonidine which affects the noradrenergic system is also used widely and has been noted to improve tics, ADHD symptoms and behaviour problems.

New and novel treatments as diverse as immunomodulatory therapy, plasmapheresis, antiobiotics, antiviral agents, melatonin, psychosurgery and even laser therapy and acupuncture, have all been reported to be successful in treating TS. These, however, have only been tried on a few patients and must be given only with the strictest of indications e. The author has no personal experience with any of these and would not recommend anyone other than experienced clinicians very well acqainted with TS to use them.

In the author's clinic, the most commonly prescribed medications to adults are sulpiride in approximately one-third of patients, followed by fluoxetine and haloperidol, and then pimozide.

Through Her Eyes

The most commonly prescribed medications to children and adolescents are clonidine in around one-third, followed by sulpiride, haloperidol and fluoxetine. Many patients with milder symptoms require no medication, but reassurance and psycho-education M. Many patients require polytherapy and thus the author prefers not to use agents such as pimozide in these instances. In addition, the author is somewhat cautious, as in the UK at least, most of the agents are neither recommended for children, nor licensed for use in TS.

TS is a truly fascinating disorder. Each patient presents the clinician with something well known and well recognized, as well as something new or unusual, which stimulates further research. Only when the putative gene s or genetic mechanisms are well defined, will some of these issues be resolved, such as the precise phenotype s. Further medication trials in better defined subgroups may then lead to improved treatments. The author wishes to thank Dr Jeremy Stern for his thoughtful comments, Dr Joe Black for helping obtain original articles, the pharmaceutical companies for supplying articles and Mr John Ludgate for his comments and support.

The basis of the treatment section of this article was first presented at the International Canadian Tourette Syndrome meeting in Quebec City, November ; thanks are given to the Canadian Tourette Syndrome Foundation for stimulating the research. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Close mobile search navigation Article navigation. History, prevalence and epidemiology. Clinical characteristics and complexities.

Tourette syndrome, associated conditions and the complexities of treatment Mary M. Brain , Volume , Issue 3, 1 March , Pages —, https: Abstract Tourette syndrome TS is characterized by multiple motor tics plus one or more vocal phonic tics, which characteristically wax and wane. Tourette syndrome , clinical phenomenology , psychopathology , treatment. School problems in Tourette's syndrome. Clonidine in neuroleptic-induced akathisia. Possible interaction between fluoxetine and pimozide causing sinus bradycardia. Nifedipine augments haloperidol in the treatment of Tourette syndrome.

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J Neurol Neurosurg Psychiatry. Gum chewing as therapy for Tourette syndrome. BNF 35, March N Engl J Med. Risperidone in the treatment of Gilles de la Tourette's syndrome — an open dose finding study. Dysphoric phenomena associated with haloperidol treatment of Tourette syndrome. J Am Acad Child Psychiatry. Subtle and underrecognized side effects of neuroleptic treatment in children with Tourette's disorder.

Risperidone as a treatment for Tourette's syndrome. The course and prognosis of Tourette syndrome. A follow-up of 78 patients with Gilles de la Tourette's syndrome. Combined pharmacotherapy risk [letter]. Viral infection and tic exacerbation [letter]. Remoxipride in adolescents with Tourette's syndrome: J Child Adolesc Psychopharmacol. Neuroimaging in child neuropsychiatric disorders. Haloperidol-induced dysphoria in patients with Tourette syndrome.

Tardive dyskinesia in persons with Gilles de la Tourette's disease [letter]. Gilles de la Tourette's syndrome, tardive dyskinesia, and psychosis in an adolescent. The trial use of clozapine for abnormal involuntary movement disorders. Tourette's syndrome in Monroe County school children. Caprini G, Melotti V. Un grave sindrome ticcosa guarita con haloperidol. Pharmacological treatment of psychiatric disorders in children and adolescents: Challas G, Brauer W. Helping patients shake off tardive dyskinesia.

Enhanced stress responsivity of Tourette syndrome patients undergoing lumbar puncture. The pharmacologic treatment of tic disorders. Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: Future therapies of Tourette syndrome. Chee KY, Sachdev P. The clinical features of Tourette's disorder: Cheng Y, Jiang DH. Paroxetine and exrapyramidal reactions. Clarke DJ, Ford R. Treatment of refractory Tourette syndrome with haloperidol decanoate.

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Comorbidity, Tourette syndrome, and anxiety disorders. Sensory phenomena associated with Gilles de la Tourette's syndrome. Clonidine ameliorates Gilles de la Tourette syndrome. Clonidine and haloperidol in Gilles de la Tourette syndrome [letter]. Guanfacine use in children with attention deficit hyperactivity disorder [letter].

Tourette syndrome and human behaviour. Tourette's syndrome and attention deficit disorder with hyperactivity: Am J Hum Genet. Embrace the endless possibilities of what this could become. I think there were several things that pulled this book from a 5 Star rating especially all the flowery writing which did have me rolling my eyes.

View all 68 comments. Mar 07, Traci Parker rated it it was amazing. This was my first time reading Ava Harrison and I can promise you it will not be my last. She sucked me in with her writing and the story told was a beautiful coming of age, finding and forgiving yourself, accepting love and one hell of an adventure. Ava's writing is a step above the norm. She is so descriptive of the surroundings that it truly makes you feel as if you are there. I walked the streets of Italy, I sailed from port to port, I smelled the sunflowers, I drank the champagne, I saw the most gorgeous sunsets.

And if her writing is not descriptive enough for you to feel like you are right there, she did an awesome first for me and tied an Instagram account to the book, prompting you at times to go see pictures that suck you even more into the journey! She sets out on a soul searching adventure. That is how she meets photographer, Chase Porter. But they both have secrets. And when those secrets are found out, the new self Aria has found falls back into the hole of despair and grief. One of my favorite things about reading is getting lost in the story, having a million different emotions and my nerves getting completely wrecked.

Ava Harrison did not disappoint!! I love that every scenario I had in my head was not true. I love that for all my guessing and contemplating, I still didn't get it and I was completely thrown for a loop with the twist Ava wrote. I love you, Ava I hate you, Ava I laughed, I swooned, I second guessed everything, I was nervous, I dreamed about it, I fell head over heels in love, my heart broke, I cried actually, I bawled , I yelled and talked to the characters and I felt so much pride and joy for the new liberated Aria! This book had it all!

View all 4 comments. Sep 23, Michelle rated it it was amazing Shelves: This was my first experience reading Ava Harrison and when I was offered a chance to read to review, I read the blurb, checked out the cover and said YES! Through Her Eyes is told in three parts; Inhale, Exhale and Breathe and these segments fit the story perfectly. We slowly get to know Aria as she takes herself on a journey of self-discovery after making a choice that changed her life forever. Running away was the easy part — find Oh my. Running away was the easy part — finding herself proved to be much more difficult.

I was falling in love with the pieces of Parker through memories and Chase was flawless as he led her on the adventure of her life. I admit that I held myself back and when I finally got sick of it, I may have abused the search feature on my Kindle and input a few names. But I realized that although I hate those urges, I needed to do it.

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I needed to be able to let go of the guessing and feel. And let me tell you about the feels. This book is packed with them. From the little messages in the postcards, to the way Chase saw her. And then when IT happens, I felt everything that Aria had felt from page one, all at once. It was a flood of emotions and I could not avoid it crashing into me. I did not expect this story to be this BIG. Being that this was my very first experience reading Ava Harrison, if this is the type of writing I can expect from her I am now a fan.

It was complex, with developed characters you easily connected with. It was gripping, emotional and the story instantly pulls you in. View all 7 comments. Mar 10, Jayme rated it really liked it Shelves: I found this book very beautiful but it isn't exactly a love story. It's about regret, finding yourself, overcome your weaknesses and go beyond your comfort zone.

It's about to stop being afraid and start living. Aria thinks of herself as a toxic girl. Her brother Owen died when they were kids. She blames herself for it. Her relationship with her parents also isn't the best. Her mother had always seen only Owen and he was the pride and joy of her parents. The person who helped her I found this book very beautiful but it isn't exactly a love story. The person who helped her get through it, is Parker, her brother's best friend. Aria for many years was in love with him, but they were just friends.

He was for her the most important person in the world. Aria blamed herself again and this time there is no one who could help her. She decides to go on a trip to Europe, a trip that was planned over the years with Parker.

Through Her Eyes by Ava Harrison

She wants to atone for her guilt and find herself again. It was during this journey she meets Chase Porter. Maybe this will be yours. This whole journey is beautiful. She visited a lot of places mainly in Italy. And then flows boat with Chase around different islands such as Ponza, Capri, Positano. Just look at the photos of these places. It is absolutely beautiful. There is a lot of descriptions of places and sightseeing, but they aren't exaggerated.

As for me the right one. You can be dreaming and want to plan your own trip. Unfortunately, when their love story should develop book is a little weaker. But only if you read to the end, you can understand everything and get to know all the answers. I have to admit that I was greatly disappointed with sexy moments, even pissed off, because I'd like them to be just as good, so if I would evaluate the same love story my ranking would have to be much lower.

But this book is about something more. He makes me believe in hope. He gives me peace. I found many fragments very close to my heart and highlight a lot of quotes that simply inspire me. But somewhere it is close to me and I think that I even needed it. But despite that sometimes there are too many of them. I wondered if they really need non-stop speak like that? Therefore, thinking about it, on the one hand, I completely in love and second, I know that it has a weak moments. Finally, I don't care because it inspired me to travel and also to find myself as well.

And I guess above all, that was exactly the point. March 16th Main characters: Aria Bennett, twenty-two, graduated student of marketing with a minor in business. Chase Porter, twenty-five, photographer, traveler. Parker, Aria's childhood best friend. He is a very important part of book. His influence on the story will be progressively revealed during the course of the plot. Especially if you like stories about traveling and finding yourself. Follow me on Facebook or Twitter. View all 14 comments. A very sweet book. This book was not my typical read. Aria is on a journey. A journey to find herself and Chase will help her do that.

May 13, 1-Click Addict Support Group rated it it was amazing. I tend to rate a book that I really liked at 4 stars. What boosts it up to a 5 star read for me is if I feel as if everyone around me needs to be experiencing it too. That was this book. I have never been in Aria's shoes. I have not dealt with her mistakes and difficult love-related decisions. I have, however, dealt with loss. She still grieved over the loss of her older brother, and I know the long term effects of a loss of that magnitude.

She also struggles with depression, not just due to a c I tend to rate a book that I really liked at 4 stars. She also struggles with depression, not just due to a clinical mental health issue, but because aspects of her life are spiraling out of control. I also related strongly to that downward spiral, and the unhealthy ways she dealt with it. Her story was told in a way that made me feel like I was in her fog of depression, which was in a way depressing, because it pulled me under with her.

It made her glimpses of hope seem just the sweeter for it, however. I also am not one to look for more in a story, not until I'm finished. So when there are twists, and when there are turns, I don't spend my time trying to guess. I allow myself to be blown away with the characters, and thus to feel their emotions right along with them. There were some real moments in this book, moments that sucked me in, moments that blew me away. I found myself desperately wishing I didn't have to put this book down. Sitting in the parking lot after my son's karate lesson, just another few minutes.

Reading while I cooked dinner, desperately grabbing those five minutes while in a waiting room. My most important recommendation for readers of this book is to slot out a piece of time, because you will not want to put it down. I found myself talking about the story to people who didn't even care. Hell, even my son. I needed to talk about it, and I didn't want to risk spoiling it for someone who had yet to read it and would.

I have already gifted my aunt a copy, and have harassed her since to finish it so that I finally have someone to discuss it with. My second recommendation is that you buddy read it with a like-minded person. You'll want to discuss it. I also loved the way it was made to tie-in with the previous books by this author. You'll have to read her first two works first, but then I loved them too so that recommendation isn't hard for me to make. It made this one feel all the more real to me, made it seem somehow even more personal. I ran the gamut with this one. From sorrow, to depression not the same emotion then to hope and despair, then to acceptance.

It's hard to try to be someone you're not, it's hard to live with the repercussions of mistakes made, and it's hard to let go of control and accept that some things are simply out of yours. Sometimes, it's even harder to accept the love you deserve. Through Her Eyes captures all of that, and paints a vivid picture while doing so.

Mar 08, Michelle rated it really liked it Shelves: ARC provided by author in exchange for an honest review Inhale. Breathe in this fresh raw, poignant, gripping and breathtaking read Through Her Eyes by Ava Harrison. In this compelling and emotionally raw story, Ava Harrison takes her readers on a journey of self discovery. She has stripped down her readers to feel the vulnerability, the sadness, the fears, the loss, the happiness, the love, and the hope.

With a wide array of emotions, readers are swept up and c ARC provided by author in exchange for an honest review Inhale. With a wide array of emotions, readers are swept up and consumed with the magnitude of a heroine finding herself. And through her eyes, we are given a fresh and provocative perspective of life, love, happiness, and second chances. With her crisp and sophisticated writing, Ava Harrison douses her readers with every facets of emotions.

This is a book that is meant to be read, experienced, and savored. Through Her Eyes is truly a fresh breath of air. Remember to inhale, exhale, and breathe everything that life throws at you. And learn from your mistakes. I know my review might be vague for some but to truly feel and enjoy this book, one must read this and experience this journey of self-discovery. Review can also be found on Four Chicks Flipping Pages: ARC kindly provided by the author in exchange for an honest review. Review to come at a later date Jul 26, Attack Salmon rated it did not like it.

This pages book feels more like pages. A whole chunk of it is about Aria exploring Europe with his new "boyfriend". If you are going to drag the whole thing out with this road trip then might as well throw in a plot twist or two. A bunch of useless description and characters messing around. Oct 20, Talon rated it it was ok. It took these people four weeks to fall madly in love with each other. My biggest peeve about this book was the dialogue. The characters spoke immaturely and very boringly to each other. He spoke in philosophical quotes that you can find on google or inspirational posters.

It was very original and boring. He also really frustrated me when it came to Parker. His lack of compassion and sympathy was a huge turn off from the get go. Aria was dull and complained literally the entire time. The book was just dull, nothing exciting happens. It was also very predictable. It could not have been over with soon enough.

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Mar 25, Samantha Schwerin rated it did not like it Shelves: I just didn't care about Aria. She seemed to be a whiny mess. Wah wah Parker loves me but I can't love him for some reason idk and then she uses her parents money to go on a trip that she and Parker had planned together to 'find herself'. I LOVE London, and yet, I barely made it through her wandering around because a she mopes and is SO melodramatic about everything b She drinks and sleeps-that's all she does. Also, I thought Parker was dead at the beginning and that would make a lot of sense, but he's not.

He's just not talking to her because Because she rejected him? But she does love him Aannd it's about Aria and some other dude. So why do I care about Parker? I certainly don't care about Aria. I am bowing out. Mar 10, Emily rated it really liked it Shelves: Aria is lost, she wants to be found. She has had two people in her life that believed in her, but circumstances tore them apart.

After another jolt leaves her to a journey of self-exploration, Aria finds herself heading on a trip that will change her life forever. Aria meets Chase Porter, a photographer who has Aria seeing life on a different level. Guilt eats at Aria, but she also sees her time with Chase as taking a much needed step into her future.

However both have secrets that could ultimate Aria is lost, she wants to be found. However both have secrets that could ultimately tear them apart. Can Aria be strong enough to fight for what she wants? This was an unusual story as with Aria you do not have all the facts. Like bread crumbs you follow Aria through her past and present. You are rooting for Aria, she has so much to fight for but first she has to believe in herself. I loved Chase, he had swagger, mystery, and a way of phrasing things that really made you think.

Apr 18, Dilek VT marked it as never-no-way. Sep 13, Patrixia Lansangan rated it really liked it. This was an adventure and it was wonderful. Sep 16, Jacquellyn rated it it was amazing. I literally had to take a deep breath when I finished this You can tell from the first pages that you don't know the whole story. There is something simmering in the background of this adventure around the world that I just couldn't quite pinpoint. I mean, I was trying to figure it out and I wasn't even close.

I also love the hero and heroine. They seemed very relatable to me. I'm jealous o 4.